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Multidetector pulmonary CT angiography: advances in the evaluation of pulmonary arterial diseases
Multidetector Pulmonary CT Angiography: Advances in the Evaluation of Pulmonary Arterial Diseases Maureen S. Filipek, MD, and Marc V. Gosselin, MD Multidetector CT (MDCT) has a primary role in the evaluation of pulmonary artery diseases. Contrast-enhanced MDCT studies are ideally suited for assessment of pulmonary arterial hypertension (PAH) and pulmonary thromboembolic disease. It has become the primary modality to diagnose acute and chronic thromboembolic disease. Its role in the evaluation of pulmonary hypertension is evolving, allowing the radiologist to assess the presence of disease and differentiating intrinsic versus extrinsic pulmonary arterial pathology. An understanding of pulmonary CT angiography, its appropriate application, associated pitfalls, contrast dynamics, and thin-section CT pulmonary and cardiac anatomy is necessary for accurate interpretation by the radiologist. In addition to assessing the pulmonary arteries MDCT has the implicit advantage of thin-section lung parenchymal imaging, a feature that often renders an alternative diagnosis when symptoms of pulmonary arterial disease occur. © 2004 Elsevier Inc. All rights reserved.
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ULTIDETECTOR CT (MDCT) has had an enormous impact in the evolution of thoracic imaging. Thoracic MDCT image capability can assess in fine detail all aspects of the thorax, including: the subsegmental 5th and 6th order pulmonary arteries, the lung parenchyma to the secondary pulmonary lobule, as well as the pleura and chest wall. The coronary arteries and cardiac pathology visualization is also rapidly evolving. The objective of this review article is to focus on MDCT angiography and the advances in imaging of the pulmonary arteries. High-resolution CT (HRCT) will not be exclusively discussed, but is vital to understand, since all MDCT have inherently thin collimation. HISTORICAL PERSPECTIVE
Conventional CT was introduced in the 1970s and was a major advancement for diagnostic thoracic imaging. Early technology produced slow scanners that limited the volume scanned during single breath hold and made contrast bolus timing difficult. Opacification of the great vessels was possible, but imaging thoracic vessels was limited. In the late 1980s single-detector CT (SDCT) helical/spiral technology was developed. Simultaneous motion of the x-ray tube and the table enabled volume acquisition over less time, which increased z-axis coverage and allowed single breath-hold imaging. Continuous helical data acquisition permitted overlapping image reconstruction without additional radiation, thus further improving z-axis resolution. The new acquisition speed also allowed for bolus timing and improved opacification of thoracic vessels. In 1992, Remy-Jardin and associates1 formally introduced pulmonary computed tomographic angiography (CTA). They assessed 42 patients and demonstrated 100% sensitivity and
96% specificity for central artery emboli (5 mm collimation was used). When increased gantry rotation speeds were developed, the collimation was reduced from 5 to 3 mm (in the same volume coverage) decreasing volume averaging and, thus, permitting improved analysis of the subsegmental arteries (Fig 1). In the late 1990s, multislice spiral CT was developed that utilized sub-second rotation times, multirow detectors, higher heat capacity tubes, improved z-axis resolution, and powerful processing systems, all leading to unprecedented speed and quality. This technology has made possible nearly motion-free CT angiograms, allowing imaging of all thoracic and cardiovascular structures in multiple orientations with sub-millimeter resolution. Standard collimation was decreased to 0.75 mm. In addition, increased scanning speeds allowed for decreased contrast volume (generally 30% less).2 Perhaps the only drawback of MDCT is the trade-off of improved resolution for increased radiation dose. Although increased doses vary with the algorithm (mA, pitch, collimation, and scanning interval), the thin collimation achieved with MDCT increases the radiation dose over SDCT for 4- and 16-slice multidetectors. Using 16-slice multidetector CT at sub-millimeter collimation can
From the Department of Radiology, Oregon Health & Science University, Portland, OR. Address correspondence to Maureen S. Filipek, MD, Oregon Health & Science University, Department of Radiology, Mail Code: L340, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098. Fax: (503) 494-4982. © 2004 Elsevier Inc. All rights reserved. 0887-2171/04/2502-0002$30.00/0 doi:10.1053/j.sult.2003.12.003
Seminars in Ultrasound, CT, and MRI, Vol 25, No 2 (April), 2004: pp 83-98
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Fig 1. Acute pulmonary emboli involving both central arteries (arrows). This examination was performed on a singlearray helical CT scanner with 3-mm collimation. Note the proximal right lower lobe pulmonary arterial enlargement, consistent with an acute embolus.
increase the radiation dose by ⬎30% over the SDCT, but is roughly equivalent to the 4-detector scanners. The increase in detector number is not directly related to increase in radiation since the Z-dose radiation efficiency is better with the 16 MDCT than with the 4 MDCT.3 POSTPROCESSING TECHNIQUES
Graphics-based software advances have allowed postscan processing, with creation of thinner slice reconstructions from the raw data and improved 3-dimensional (3D) renderings. Instantaneous multiplanar reformatting techniques generated from MDCT axial cuts are leading to some of the most practical and exciting applications in thoracic imaging, particularly in evaluation of the pulmonary vasculature. This topic was thoroughly discussed in the recent literature.4-7 Four different forms of postprocessing techniques are commonly used today, each with advantages and pitfalls. Two-dimensional multiplanar reconstructions (MPR) with curved reformations can be performed quickly on workstations or on most PACS stations. MPR results in coronal and sagittal reformations that help define the craniocaudad extent of disease and better define regions of stenosis or embolization. Oblique and curvilinear views are also possible (Fig 2). Maximum intensity projections (MIPs) select out data in a given Hounsfield unit (HU) attenua-
Fig 2. Superior vena cava and pulmonary artery thrombus. (A) Right pulmonary artery embolus is evident (small arrow), along with left lower lobe atelectasis from mucus plugging. The SVC has a persistent filling defect (large arrow) that, at the time of examination, did not change from image to image, suggesting thrombus. (B) Coronal reformations confirm the presence of SVC thrombus (arrow) and demonstrate its craniocaudad extent. The thrombus originated in the left subclavian vein (not shown here).
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tion range and discard the data outside of the range. MIP is particularly helpful in displaying small volumes to further define anatomic relationships. Misrepresentation (under- and overrepresentation) errors occur more frequently with this application, especially in regions of superimposing structures (Fig 3). 3D shaded surface display (SSD) rendering techniques can create images of the vessels by choosing an HU range of the contrast medium. However, if this range is inaccurate, artificial narrowing or minimization of a stenosis can occur. Stairstep artifacts occur with this postprocessing technique, but are less of a problem with the improved z-axis coverage and thinner collimation achieved with MDCT. SSD remains a useful postprocessing method for osseous evaluation, but is not often utilized for the pulmonary vessels (Fig 4). 3D volume rendered images are the most reliable of the postprocessing techniques for vascular structures. This method uses all the data in creating final images, and is therefore more accurate (less user dependent), and has essentially replaced the
Fig 4. Shaded surface display of a patient’s ribs and scapula. Fractures are present in the left 4th through 9th ribs (arrows). This 3D representation is easy to perform, but currently has limitations with vascular imaging, and has been replaced by MIP and volume rendering techniques.
SSD. 3D volume rendering can change the shading characteristics of structures, which allows “fly through” endoluminal imaging capability. Any imaging plane can be viewed on the workstation. The thoracic anatomy can be reconstructed into a number of different presentations to highlight a particular abnormality (Fig 5). ACUTE PULMONARY ARTERIAL THROMBOEMBOLIC DISEASE
Fig 3. Incidental diagnosis of patent ductus arteriosis. A 4-mm MIP reformation of the thoracic aorta shows a small patent ductus arterosis. MIP images can “summarize” information from numerous axial scans.
Pulmonary embolus (PE) is a common event in the hospital setting. It occurs from central migration of a clot formed in the deep venous structures of the legs, pelvis, or abdomen. Deep vein thrombosis most commonly occurs secondary to prolonged stasis, trauma, or underlying hypercoaguable state. Diagnosis of PE is imperative, since undiagnosed PE is associated with high mortality.8,9 Excluding PE is also important, because long-term anticoagulation can result in serious bleeding complications.
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Fig 5. Volume rendering. (A) Severe mosaic perfusion is demonstrated with volume rendering of the lungs. The brighter areas representing increased blood flow. Of interest, this pattern matched the perfusion scan performed by nuclear medicine the previous day (not shown). (B) Volume rendering of the patient in Figure 3, demonstrating the patent ductus arteriosis (arrow). (Color version of figure is available online.)
Historically, nuclear medicine ventilation-perfusion (V/Q) scintigraphy, leg vein ultrasound, and pulmonary angiography were the mainstay for evaluating pulmonary embolus. The largest prob-
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lem with V/Q scans is the majority of patients studied (40-60%) fall into an intermediate/indeterminate probability scan (nondiagnostic), with fewer falling in a more definitive high or low probability category. V/Q scans can aid in diagnosis only when they are normal (4-40%) or high probability (10-20%).10-13 Lower extremity venous ultrasound for deep vein thrombosis is noninvasive and relatively inexpensive. However, less than half of the patients with angiographically proven PE have a positive exam.14 This means that patients with a high clinical suspicion for PE, with a nondiagnostic V/Q scan and a negative venous leg ultrasound, still require additional diagnostic studies. Even patients with a low clinical suspicion of embolus and a high probability V/Q scan require further evaluation, since only about 55% of these patients have a proven embolus by angiography.11 Prior to CTA, pulmonary angiography was the only examination that directly visualized the pulmonary arteries. The invasiveness and cost of this method are undesirable, as reflected in the practice patterns of clinicians, who rarely ordered the examination despite nondiagnostic V/Q scans.15 Additionally, studies have also shown limitations of pulmonary angiograms in the assessment of the subsegmental arterial branches.16 The PIOPED study demonstrated 66% interobserver variability in diagnosis of subsegmental thrombus, suggesting a number of these small emboli were missed. The significance of these small emboli is controversial, since a “negative” angiogram had excellent results, with only 1.7% subsequent embolic events over 6 months.17 One-year follow-up on negative CTAs has shown a similar low rate of embolic events (2%).18 With the development of single-slice spiral CT came the first opportunity to image the central and segmental pulmonary arteries within the 40-s duration of a peripheral IV contrast injection. Perhaps more importantly, in addition to assessing the pulmonary vasculature, CT offered complete evaluation of the lung parenchyma, which has led to an alternate intrathoracic diagnosis in as many as 30-60% of those studied for PE.12,19 The development of 4-row multislice scanners and 16-row multislice scanners has allowed even thinner section collimation to be used, providing improved images of subsegmental, and even 5th order, pulmonary arteries with increased sensitivity and specificity. Ghaye and colleagues20 showed that
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Fig 6. Improved visualization of an acute left lower lobe subsegmental embolus with increasingly narrow collimation. (A) 5-mm collimation, (B) 3-mm collimation, and (C) 1.5-mm collimation. As the collimation narrows, there is decreasing partial volume and improved z-axis resolution.
using 1-mm-thick reconstructed scans, 98% of subsegmental arteries are adequately analyzed, as are 74% of 5th order pulmonary arteries (Fig 6). Pulmonary CTA is now unequivocally superior to V/Q imaging in the diagnosis of pulmonary embolus, especially in patients with abnormal chest radiographs. A 1997 prospective study comparing V/Q scans with CTA showed spiral CTA to have a sensitivity of 87% and specificity of 98% in the diagnosis of acute PE compared with a sensitivity of 41%, and a specificity of 52% for a high-probability V/Q scan.10,21 This undoubtedly underestimates current sensitivity and specificity of CTA, given the technological progression of CTA resolution (MDCT) in the 5 years since this study. The limited imaging quality with thin-collimation, single-detector CT created controversy regarding the accuracy of pulmonary CTA versus pulmonary angiography.22 The sensitivity of single-detector pulmonary CTA for detection of PE has ranged widely in literature reports (between
Fig 7. The 2-mm collimation on this examination demonstrates an axial right upper lobe apical subsegmental acute embolus (arrow). Subsegmental and axial vessels are more consistently seen with the improved z-axis coverage.
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due to respiratory artifacts associated with severe dyspnea. MDCT IMAGING OF ACUTE THROMBOEMBOLIC DISEASE
Utilizing mediastinal (soft tissue) windows, pulmonary arterial filling defects are seen in acute pulmonary embolus. These may be central, marginal, or complete. Acute or subacute central filling defects form an acute angle with the vessel wall, which has been shown to be the most reliable indicator of pulmonary embolus.24 Confirming that the filling defect is arterial (versus venous) can be easily accomplished by switching to lung windows to demonstrate the accompanying bronchus or by
Fig 8. Chronic PE findings. (A) Bilateral proximal lower lobe arterial webs (arrows) from recurrent embolic events 1 year ago. (B) Right lower lobe web with calcification (arrow).
80% and 100%). The range likely reflects the evolution of CTA techniques in the past 10 years. In 2000, double-array CTA was compared to conventional angiography in a prospective study of 157 patients.23 There was no significant difference in the rate of suboptimal studies between dual-slice CT (7%) and selective pulmonary angiography (6%). Compared to selective pulmonary angiography, dual-array CT demonstrated 94% specificity and 90% sensitivity. Additionally, more central and subsegmental emboli were found by CTA than with conventional angiography (Fig 7). Past investigators have reported a 2-4% suboptimal study rate with CTA for acute PE.5 This figure is comparable to the 3% suboptimal rate of pulmonary angiography reported in the PIOPED trial.11 Suboptimal examinations are most often
Fig 9. Chronic PE findings. (A) A distal left main PA mural thrombus is present (arrow), with associated pulmonary arterial enlargement and hypertension. Note the irregular inner border of the thrombus, which distinguishes it from a lymph node. (B) The lungs demonstrate mosaic perfusion from the chronic thromboembolic disease and hypertension. Note the enlarged and more numerous pulmonary vessels in the higher density areas.
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ated calcification. Rarely, pulmonary arterial dissection has been shown to occur. As opposed to acute emboli, chronic emboli show no expansion of the vessels. The involved peripheral vessels attenuate, taper, or develop stenosis.25 Centrally, PAH is often seen and is further described below. High-resolution lung parenchymal findings of chronic pulmonary embolic disease include mosaic lung attenuation. Mosaic attenuation shows geographic regions of higher attenuation with scattered lucent regions. The higher attenuation regions have normal perfusion and the lucent (abnormal) regions have decreased perfusion with attenuation of both vessel size and number26 (Fig 9). PULMONARY MDCTA PITFALLS
False negative examinations are variable, but well known in the literature with SDCT. The rate is
Fig 10. Breathing artifact. (A) The right and left upper lobe segmental vessels demonstrate apparent partial filling defects, thought to represent emboli. (B) The lung windows at this same image show moderate respiratory motion. A repeat examination involving this region of the lung was performed before the patient left the table. These vessels were clear of emboli and therefore the filling defects were secondary to motion-related partial volume artifacts.
following the course of the vessel. Expansion of the vessel in acute emboli is a common and important ancillary finding (Fig 1). Nonopacified vessels without expansion are nondiagnostic, just as with angiography. Lung parenchymal findings of PE include wedge shaped, peripheral consolidation, representing an area of hemorrhage or possibly infarct. CHRONIC THROMBOEMBOLIC DISEASE
Chronic thromboembolic disease has several characteristic features. Mature emboli often form webs, stenosis, or areas of recanalization within the pulmonary artery (Fig 8). Mural thrombus is often seen adherent to the wall, with occasional associ-
Fig 11. Sharp algorithm artifact. (A) CTA reconstructed with a sharp algorithm demonstrates multiple low-density central filling “defects” involving all vessels within the lower lobes. Both arteries and veins are involved. The decrease in density is not as low as expected for emboli, with the exception of the right lower lobe posterior segmental branch. (B) The same image with a soft algorithm shows the right lower lobe posterior segmental embolus (arrow). The remainder of the low-density central “defects” were related to an artifact from the sharp algorithm.
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results in apparent termination of vessels or volume averaging with adjacent lung, mimicking filling defects. This artifact should be suspected by appreciating the same vascular image degradation throughout all the vessels on the same image. Viewing the same slice in lung windows will demonstrate the concurrent parenchymal motion and blurring (Fig 10). Bolus delay time is crucial for proper opacification of the arteries needed for identifying filling defect. The scan delay must be optimized for contrast arrival at the target vessels. Bolus timing depends on the cardiac output. Acquiring the images too early in the bolus results in inadequate vessel enhancement and a decreased ability to differentiate clot from surrounding blood. Imaging of the bolus too late may lead to inadequate vessel contrast enhancement toward the end of the examination.28 Reviewing CTA in a sharp (lung) algorithm results in an artificial central low density within vessels, which may lead to a false diagnosis of PE. This artifact can be recognized, since it appears at the same level throughout all the
Fig 12. Nodal tissue versus thrombus. (A) Lymph nodal tissue located at the bifurcation of left main pulmonary artery. Note the smooth inner border, which helps distinguish it from a small mural thrombus. (B) Chronic right pulmonary artery mural thrombus, which has a smooth outer border.
less with MDCT, given the increased speed and thinner collimation of this method. Though there has been little written about the actual false positive rate with SDCT or MDCT, there are numerous potential pitfalls described in the literature that result in an indeterminate scan, or possibly a false positive exam.19,27 Pitfalls can be classified as technical, physiologic, or anatomic in nature. An understanding of these interpretive pitfalls is vital for the radiologist to recognize pulmonary embolus mimics, and to reduce the false positive rate. Technical pitfalls include respiratory motion artifact, improper bolus delay, and reviewing images in a sharp algorithm. Respiratory motion artifact
Fig 13. Mucus-filled bronchus. (A) In the right lower lobe, a low-density mucus plug (arrow) is seen adjacent to the posterior segmental artery. (B) This was confirmed on the lung windows, which demonstrate multiple areas of mucus plugging and concurrent thickening of the airways.
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Fig 14. Inspiration-associated interruption of contrast. (A) The initial images at the base of the heart and lower lobe vessels demonstrate opacification of the right ventricle and pulmonary arteries. These images were obtained immediately after deep inspiration. (B) Unopacified blood enters from the IVC, diluting the contrast column within the right heart. Normal opacification is present in the left ventricle and pulmonary veins. (C) Severe decrease in density is present involving the right ventricle and pulmonary arteries, leading to a false positive diagnosis of pulmonary embolus. (D) Images at the level of the main pulmonary artery show return of the normal opacification. This interruption of the contrast bolus is a common finding, though usually it is milder in severity.
arteries, and often the veins as well. The relative decrease in density is not as severe as that seen with embolic defects and there is no vascular expansion. The central low density is thought to result from a sharpening artifact, potentially from laminar flow. To avoid this artifact, all vascular evaluation should be conducted in a soft tissue algorithm. Figure 11 compares the appearance of the pulmonary arteries in sharp and soft algorithms. Streak artifact and beam hardening around the superior vena cava can also mimic thrombus within the apical segment of the right upper lobe
artery and main right pulmonary artery, creating diagnostic problems in these areas. Some authors have advocated the use of a postcontrast saline flush to dilute the end of the bolus and reduce this artifact.29 Normal anatomic structures, such as veins, lymph nodes, axial vessels, and mucus plugging, can mimic PE. Intrapulmonary lymph nodes are not usually rounded in shape, but usually are more elongated and flat in appearance. Knowledge of the size and location of pulmonary hilar lymph nodes is crucial, because they are seen as low-density structures adjacent to vessels and may mimic in-
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Table 1. Clinical Classification of Pulmonary Hypertension* 1. Precapillary pulmonary arterial hypertension (a) Primary pulmonary hypertension Sporadic Familial (b) Related to Collagen vascular disease Congenital systemic to pulmonary shunts Portal hypertension HIV infection Drugs/toxigens (anorexigens and others) Persistent pulmonary hypertension of the newborn 2. Pulmonary venous hypertension (a) Left-sided atrial or ventricular heart disease (b) Left-sided valvular disease (c) Pulmonary veno-occlusive disease (d) Extrinsic compression of central pulmonary veins Fibrosing mediastinitis Adenopathy/tumor 3. Disorders of the respiratory system and/or hypoxemia (a) Chronic obstructive pulmonary disease (b) Interstitial lung disease (c) Sleep disordered breathing (d) Alveolar hypoventilation disorders (e) Chronic high altitude exposure (f) Neonatal lung disease (g) Alveolar-capillary dysplasia 4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease (a) Thromboembolic obstruction of proximal pulmonary arteries (b) Obstruction of distal pulmonary arteries Pulmonary embolism (thrombus, tumor, ova and/or parasites, foreign material In situ thrombosis Sickle cell disease 5. Pulmonary hypertension due to disorders directly affecting the pulmonary vasculature (a) Inflammatory Schistosomiasis Sarcoidosis (b) Pulmonary capillary hemangiomatosis *From the 1998 World Symposium on Primary Pulmonary Hypertension.35
traluminal marginal filling defects, especially at vessel bifurcations. Lymph nodes can be differentiated from mural thickening (chronic PE), since the lymph nodes have a smooth inner border while chronic thrombus has a smooth outer border, as seen in Figure 12. Mucus plugging is a common abnormality, and is a well-described diagnostic pitfall occasionally leading to misdiagnosis of PE. Mucus plugging can be recognized by identifying an enhancing vessel next to the filled bronchus and by the absence of a lucent airway on lung windows (Fig 13). Multiplanar reformations also can aid in the anatomical discrimination of the bronchus and artery. There are also physiological circumstances that can lead to a false diagnosis of emboli.30,31 Patent foramen ovale or atrial septal defect may permit opacified blood to escape from the right atrium into the systemic circulation, decreasing the contrast level in the pulmonary arteries to nondiagnostic levels. Such intracardiac shunts are indicated by initial high level of opacification of the aorta, possibly exceeding that of the pulmonary artery. A second physiologic problem is transient interruption of the contrast column occurring with deep inspiration at the beginning of the examination, which causes the inflow of unopacified blood into the right heart chambers from the IVC.28,30,31 Inflow of unopacified blood generally occurs in patients with normal right heart pressures and appears as a short, uniform decrease in arterial opacification, without vascular expansion (Fig 14). Characteristically, this contrast defect is observed in all pulmonary arteries at the same level. Another important clue is the presence of decreased opacification within the right heart chambers just before the contrast deficit occurs within the pulmonary arteries.
Table 2. Causative Physiologic Alterations for Developing Pulmonary Arterial Hypertension Physiologic Etiology for PAH
Increased flow Chronic hypoxia Vessel obliteration Chronic pulmonary venous hypertension
Examples
Atrial septal defect, ventricular septal defect, transposition of great vessels, common atrio/ventricular canal, partial anomolous venous return Chronic bronchitis, bronchiolitis obliterans, advanced pulmonary fibrosis, sleep apnea, cystic fibrosis, chronic high altitude exposure Emphysema, primary pulmonary hypertension, chronic thromobembolic disease, vasculitis, sickle-cell disease, schistosomiasis, tumor emboli Left ventricular or atrial disease, left-sided valvular disease, pulmonary venoocclusive disease, and capillary hemangiomatosis
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1. primary pulmonary hypertension, 2. pulmonary venous hypertension, 3. pulmonary hypertension associated with disorders of the respiratory system and/or hypoxemia, 4. pulmonary hypertension due to thromboembolic disease, and
Fig 15. Enlargement of the main pulmonary artery is defined as greater than the ascending aorta, as clearly seen here, or >29 mm. A small amount of mural thrombus is seen along the left distal main pulmonary artery (arrow).
PULMONARY ARTERIAL HYPERTENSION
Normal pulmonary arteries have three layers, ie, a single layer of endothelial cells, a medial smooth muscle layer, and an outer adventitial layer. The large elastic arteries have diameters greater than 0.5 mm and accompany an adjacent bronchiole to the subsegmental level. Distal to this, they transition to muscular arteries, which accompany the terminal bronchioles. As the artery travels peripherally it becomes an arteriole with a thinner smooth muscle layer. The arteriole caliper further diminishes and continues with the respiratory bronchiole to form a terminal capillary network in the alveolar walls. PAH, regardless of cause, is a severe disease with a dismal natural outcome. The symptoms of pulmonary hypertension can be illusive and nonspecific (dyspnea and fatigue) and this frequently delays diagnosis until the disease is advanced.32 Current therapies for PAH are limited, and include lung transplantation and intravenous prostacyclin (arterial dilator).33 PAH is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest as determined with right heart catheterization. (Normal pulmonary arterial wedge pressure is ⬍12 mmHg.32) Pulmonary hypertension secondary to known cardiac, pulmonary, or hepatic disease is far more common than primary pulmonary hypertension where there is no identifiable cause. The World Health Organization has classified PAH into the following five types:34
Fig 16. (A) Right ventricular hypertrophy. The thickness of the right ventricular wall (arrows) is excessive. Normally the wall thickness should not exceed 4 mm. The interventricular septum does not demonstrate the normal mild bowing toward the right ventricular chamber. Mild dilation of the right atrium and IVC is also present. (B) Coronal reformation demonstrates chronic thromboembolic disease (arrows) along with reflux of contrast into the IVC and hepatic veins.
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5. pulmonary hypertension due to disorders directly affecting the pulmonary vasculature (Table 1). Others have described pulmonary hypertension by the location of the defect or process relative to the capillary bed (precapillary, capillary, and postcapillary).35 We find it practical to categorize PAH etiology by four basic underlying physiologic alterations that represent the most common causes for pulmonary hypertension: increased flow (left to right shunt), chronic hypoxia, vessel obliteration, and chronic pulmonary venous hypertension (Table 2). PRIMARY AND SECONDARY PAH IMAGING FINDINGS
MDCT has a primary role in diagnosing PAH and identifying possible causes. MDCT can discriminate a primary lung parenchymal disease (fibrosis or small airways disease) or a primary cardiac process (septal defects, valvular disease, or myocardial failure) as the main contributing factor to PAH, as opposed to an intrinsic pulmonary vascular disease. MDCT imaging can concurrently assess the state of the right ventricle and assess for cor pulmonale. It is important, when possible, to identify chronic pulmonary venous hypertension as the predominant physiological etiology of PAH, as treating postcapillary processes with prostacyclin can result in a deleterious outcome from worsened or fatal pulmonary edema.33 Tan et al36 concluded, in their retrospective study, that a main pulmonary artery diameter of 29 mm or greater identifies patients with even mild PAH. Others have described a larger transverse pulmonary artery diameter than the adjacent ascending aorta as evidence of PAH (Fig 15). Measurement of the right and left intrapericardial portions of the pulmonary arteries has also been described in evaluating PAH. They are considered enlarged if their diameter is ⬎18 mm at 1-cm distance from their origin.37 Enlargement of the lobar arteries to a greater diameter than the accompanying bronchus is also a useful sign (for conventional radiographs as well). Right heart disease is a common and expected secondary finding of PAH due to the increased workload of the right heart. The increased pressure transferred to the right heart results in right-sided enlargement and hypertrophy. Right atrial enlargement is defined as ⬎35 mm in transverse diameter, and right ventricle enlargement is defined as ⬎45
mm in transverse diameter.33,37 At times, the elevated right ventricular pressures (end diastolic pressure) is severe enough to cause bowing of the interventricular septum toward the left ventricle38 (Fig 16). The inferior vena cava is also frequently dilated. Elevated end diastolic right heart pressures can be hemodynamically observed through contrast bolus dynamics. Elevated right heart pressures cause reflux of hyperdense contrast into the IVC and the hepatic veins28 (Fig 17). Constrictive pericarditis and right heart failure (with normal pulmonary arteries) can also demonstrate IVC reflux and must be excluded as a cause. When there is clinical or radiographic evidence of elevated right heart pressures, it is prudent to perform a CT timing bolus, since pulmonary artery opacification may be quite delayed by decreased right ventricular outflow. The absence of venous reflux, or the presence of unopacified mixing in the right heart chambers from a decompressed IVC, argues against any significant elevation of right heart pressures and concurrently the presence of PAH. Assessing the diameter and distribution of the pulmonary veins/venous flow aids in diagnosing postcapillary pulmonary hypertension. Enlarged pulmonary veins and cephalization indicate chronic pulmonary venous hypertension secondary to left-sided heart disease, often with concurrent dilation of left heart chambers. Septal thickening is an occasional concurrent imaging manifestation in chronic venous hypertension39 (Fig 18).
Fig 17. Hyperdense reflux of contrast into the dilated IVC and hepatic veins. This contrast flow is often seen in patients with elevated right atrial and ventricular pressures. In this case, the patient had markedly elevated pulmonary artery pressures.
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UNUSUAL CAUSES OF PULMONARY ARTERIAL HYPERTENSION
Pulmonary veno-occlusive disease is an uncommon disorder, which is caused by the gradual obliteration of pulmonary veins. Intimal proliferation and fibrosis of the veins are found on pathology. The chronic elevation of the venous pressures eventually leads to PAH. Multiple etiologies are associated with this pathological process. The prognosis is poor, with progression of symptoms and death often over a few years. The most common MDCT findings are ground glass opacification, interlobular septal thickening, pleural and pericardial effusion, and no enlargement of left
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heart chambers (Fig 18). This latter finding helps distinguish pulmonary veno-occlusive disease from the more common cardiac causes of pulmonary venous hypertension.5,33,40 Pulmonary capillary hemangiomatosis is a rare cause of PAH, representing the proliferation of thin-walled capillary-like vessels, which invade the veins and arterioles. It is associated with intimal fibrosis, hemorrhage, and venous stenosis. The etiology is unknown, but it may represent a form of low-grade malignancy or metastatic dissemination of an angiosarcoma. MDCT imaging, clinical course, and prognosis are similar to pulmonary veno-occlusive disease.5,33,40
Fig 18. Pulmonary veno-occlusive disease. A 55-year-old male with progressive worsening dyspnea and recurrent episodes of “heart failure.” (A) Enlarged pulmonary artery, consistent with hypertension. (B) Right ventricular hypertrophy and a straightened interventricular septum. However, the left ventricle does not demonstrate any dilation or hypertrophy. (C) Bilateral ground glass opacity and septal thickening. This latter finding is consistent with a postcapillary pathology, but the normal appearing left ventricle and left atrium (not shown) suggest that the problem is not cardiac. Open lung biopsy demonstrated pulmonary veno-occlusive disease.
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Fig 19. Arterial tumor embolization. A 48-year-old male with progressive dyspnea over the last 4 weeks. (A) Widespread “tree-in-bud” opacities are present, suggestive of an active inflammatory process in the bronchioles. (B) Expiratory images did not show any air trapping, which is not consistent with small airways disease (ie, respiratory bronchial inflammation). (C) Contrast-enhanced image though the heart demonstrates a large mass arising in the right atrium and ventricle. Open lung biopsy showed numerous tumor emboli and lymphangitic spread of tumor along the distal arteries from the patient’s cardiac angiosarcoma.
Pulmonary arterial tumor embolism often presents with progressive dyspnea due to PAH. It is a difficult diagnosis to make clinically, requiring a high clinical suspicion. Intravascular embolic disease on MDCT is usually manifested with numerous branching vascular “tree-in-bud” opacities with a beaded appearance (Fig 19). Peripheral areas of infarction have been described.41 The importance of expiratory images has not been emphasized in these rare cases. The presence of treein-bud opacities usually is secondary to filling of the terminal bronchioles with an active inflammatory process. Focal air trapping is often seen in the
areas of greatest involvement. Absence of airtrapping should suggest that the tree-in-bud opacities may not be located within the terminal bronchioles, and other diseases, such as tumor emboli, should be considered. CONCLUSION
The evaluation of pulmonary embolus and pulmonary arterial hypertension is greatly expanding application of MDCT. The improved contrast-enhanced imaging is allowing for more refined diagnoses and characterization of PAH and thromboembolic disease. This article and recent similar
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publications aim to increase insight and knowledge of this rapidly progressing modality. The radiologist’s knowledge of appropriate pulmonary MDCT
use, pulmonary MDCTA pitfalls, contrast dynamics, and high-resolution anatomy is essential for optimal image interpretation.
REFERENCES 1. Remy-Jardin M, Remy J, Wattinne L, et al: Central pulmonary thomboembolism: Diagnosis with spiral volumetric CT with a sing-breath-hold technique. Comparison with pulmonary angiography. Radiology 185:381-387, 1992 2. Remy-Jardin M, Mastora I, Masson P, et al: Multislice CT of the thorax with reduced volume of contrast material: A comparative study with CT. Eur Radiol 11P:167, 2001 3. Ryberg J, Liang Y, Teague S: Fundamentals of multichannel CT. Radiol Clin N Am 41:465-474, 2003 4. Raven JG, McAdams HP: Multiplanar and three-dimensional imaging of the thorax. Radiol Clin N Am 41:475-489, 2003 5. Remy-Jardin M, Remy J: Spiral CT angiography of the pulmonary circulation. Radiology 212:615-636, 1999 6. Muller NL: Computed tomography and magnetic resonance imaging: Past, present, and future. Eur Respir J 19(Suppl 35):3s-12s, 2002 7. Remy J, Remy-Jardin M, Artaud D, et al: Multiplanar and three-dimensional techniques in CT: Impact on chest disease. Eur Radiol 8:335-351, 1998 8. Lorut C, Ghossains M, Horellou MH, et al: A noninvasive diagnostic strategy including spiral computed tomography in patients with suspected pulmonary embolism. Am J Respir Crit Care Med 162(4 Pt 1):1413-1418, 2000 9. Goldhaber SZ: Modern treatment of pulmonary embolism. Eur Respir J 19(Suppl 35):22s-27s, 2002 10. van Rossum AB, Pattynama PM, Ton ER, et al: Pulmonary embolism: Validation of spiral CT angiography in 149 patients. Radiology 201:467-470, 1996 11. PIOPED Investigators: Value of ventilation-perfusion scans in acute pulmonary embolism: Result of the prospective investigation of pulmonary embolism diagnosis. JAMA 263: 2753-2759, 1990 12. Hull RD, Raskub GE, Carter CJ, et al: Pulmonary embolism in outpatients with pleuritic chest pain. Arch Intern Med 148:838-844, 1988 13. Sostman HD, Coleman RE, Delong DM, et al: Evaluation of revised criteria for ventilation-perfusion scintigraphy in patients with suspected pulmonary embolism. Radiology 193: 103-107, 1994 14. Hull Rd, Raskub GE, Coates F, et al: A new noninvasive strategy for patients with suspected pulmonary embolism. Arch Intern Med 149:2549-2556, 1989 15. Goodman LR, Curtin JJ, Mewissen MW, et al: Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: Helical CT versus angiography. AJR 164:1369-1374, 1995 16. Pond GD, Ovitt TW, Capp MP: Comparison of conventional pulmonary angiography with interventional digital subtraction angiography for pulmonary embolic disease. Radiology 147:345-350, 1983 17. Novelline RA, Baltarowich OH, Athanasoulis CA, et al: The clinical course of patients with suspected pulmonary embolism with a negative pulmonary angiogram. Radiology 126: 561-567, 1978
18. Tillie-Leblond I, Mastora I, Radenne F, et al: Risk of pulmonary embolism after a negative spiral CT in patients with pulmonary disease: A one-year clinical follow-up study. Radiology 223:461-467, 2002 19. Herold CJ: Spiral computed tomography of pulmonary embolism. Eur Respir J Suppl 35:13s-21s, 2002 20. Ghaye B, Szapiro D, Mastora I, et al: Peripheral pulmonary arteries: How far in the lung does multi-detector row spiral CT allow analysis? Radiology 219:629-663, 2001 21. Mayo JR, Remy-Jardin M, Muller NL, et al: Pulmonary embolism: Prospective comparison of spiral CT with ventilation-perfusion scintigraphy. Radiology 205:447-452, 1997 22. Bile EM, King GG, Muller NL, et al: Spiral computed tomography is comparable to angiography for diagnosis of pulmonary embolism. Am J Respir Crit Care Med 161:10101015, 2000 23. Qanadli SD, Hajjam ME, Mesurolle B, et al: Pulmonary embolism detection: Prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. Radiology 217:447-455, 2000 24. CT Angiography of the Chest, in Remy-Jardin M, Remy J, Mayo J, et al: Acute Pulmonary Embolus. Philadelphia, PA, Lippincott Williams and Wilkins, Ch 4, pp 51-65 25. King M, Ysreal M, Begin C: Chronic thrombembolic pulmonary hypertension: CT Findings. AJR 170:955-960, 1998 26. Webb R, Mu¨ ller N, Naidich D: High-Resolution CT of the Lung (3rd ed). Pulmonary Hypertension and Pulmonary Vascular Disease. Ch 9, pp 547-568 Philadelphia, PA, Lippincott Williams and Wilkins, 2001 27. Remy-Jardin M, Mastora I, Remy J: Pulmonary embolus imaging with multislice CT. Radiol Clin North Am 41:507-519, 2003 28. Gosselin M, Rubin G: Altered intravascular contrast material flow dynamics: Clues for refining thoracic CT diagnosis. Pictorial Essay. AJR 169:1597-1603, 1997 29. Hsu RM: Computed tomographic angiography: Conceptual review of injection and acquisition parameters with a brief overview of rendering techniques. Appl Radiol 31:33-39, 2002 30. Henk CB, Grampp S, Linnau KF, et al: Suspected pulmonary embolism: Enhancement of pulmonary arteries at deep-inspiration CT angiography—Influence of patent foramen ovale and atrial-septal defect. Radiology 226:749-755, 2003 31. Gosselin M, Rasser U, Thesizon S, et al: Contrast Dynamics During CT Pulmonary Angiogram: Analysis of an Inspiration Associated Artifact. J Thorac Imaging 19(1):1-7, 2004 32. Mu¨ ller, Fraser, Colman, Pare: Diagnosis of Diseases of the Chest, 4th ed. Chapter 13: Pulmonary Hypertension. Philadelphia, PA, WB Saunders Company 2001, pp 410-431 33. Resten A, Maitre S, Humbert M, et al: Pulmonary arterial hypertension: Thin-section CT predictors of epoprostenol therapy failure. Radiology 222:782-788, 2002 34. Rich S (ed). World Health Organization: Primary Pulmonary Hypertension. Executive Summary. World Symposium
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Primary Pulmonary Hypertension 1998. Available at: http:/ www.who.int/ncd/cvd/ppn.html 35. Wagnevoort CA: Classifying pulmonary vascular disease. Chest 64:503-504, 1973 36. Tan RT, Kuz OR, Goodman LP, et al: Utility of CT scan evaluation for predicting pulmonary hypertension in patients with parenchymal lung disease. Chest 113:125-1256, 1998 37. O’Callaghan JP, Heitzman RE, Somogy JW, et al: CT evaluation of pulmonary artery size. J Comput Assist Tomogr 6:101-104, 1982 38. Oliver T, Reid JH, Murchism JT: Interventricular septal shift due to massive pulmonary embolism shown by CT pul-
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monary angiography: An old sign revisited. Thorax 53:10921094, 1998 39. Primack SL, Muller NL, Mayo JR, et al: Pulmonary parenchymal abnormalities of vascular origin: HRCT findings. Radiographics 14:739-746, 1994 40. Dufour B, Maitre S, Humbert M, et al: High-resolution CT of the chest in four patients with pulmonary capillary hemangiomatosis or pulmonary veno-occlusive disease. AJR 171:1321-1324, 1998 41. Shepard JA, Moore EH, Templeton PA, et al: Pulmonary invasive tumor emboli: Dilated and beaded peripheral pulmonary arteries at CT. Radiology 187:797-801, 1993
M
ULTIDETECTOR CT (MDCT) has had an enormous impact in the evolution of thoracic imaging. Thoracic MDCT image capability can assess in fine detail all aspects of the thorax, including: the subsegmental 5th and 6th order pulmonary arteries, the lung parenchyma to the secondary pulmonary lobule, as well as the pleura and chest wall. The coronary arteries and cardiac pathology visualization is also rapidly evolving. The objective of this review article is to focus on MDCT angiography and the advances in imaging of the pulmonary arteries. High-resolution CT (HRCT) will not be exclusively discussed, but is vital to understand, since all MDCT have inherently thin collimation. HISTORICAL PERSPECTIVE
Conventional CT was introduced in the 1970s and was a major advancement for diagnostic thoracic imaging. Early technology produced slow scanners that limited the volume scanned during single breath hold and made contrast bolus timing difficult. Opacification of the great vessels was possible, but imaging thoracic vessels was limited. In the late 1980s single-detector CT (SDCT) helical/spiral technology was developed. Simultaneous motion of the x-ray tube and the table enabled volume acquisition over less time, which increased z-axis coverage and allowed single breath-hold imaging. Continuous helical data acquisition permitted overlapping image reconstruction without additional radiation, thus further improving z-axis resolution. The new acquisition speed also allowed for bolus timing and improved opacification of thoracic vessels. In 1992, Remy-Jardin and associates1 formally introduced pulmonary computed tomographic angiography (CTA). They assessed 42 patients and demonstrated 100% sensitivity and
96% specificity for central artery emboli (5 mm collimation was used). When increased gantry rotation speeds were developed, the collimation was reduced from 5 to 3 mm (in the same volume coverage) decreasing volume averaging and, thus, permitting improved analysis of the subsegmental arteries (Fig 1). In the late 1990s, multislice spiral CT was developed that utilized sub-second rotation times, multirow detectors, higher heat capacity tubes, improved z-axis resolution, and powerful processing systems, all leading to unprecedented speed and quality. This technology has made possible nearly motion-free CT angiograms, allowing imaging of all thoracic and cardiovascular structures in multiple orientations with sub-millimeter resolution. Standard collimation was decreased to 0.75 mm. In addition, increased scanning speeds allowed for decreased contrast volume (generally 30% less).2 Perhaps the only drawback of MDCT is the trade-off of improved resolution for increased radiation dose. Although increased doses vary with the algorithm (mA, pitch, collimation, and scanning interval), the thin collimation achieved with MDCT increases the radiation dose over SDCT for 4- and 16-slice multidetectors. Using 16-slice multidetector CT at sub-millimeter collimation can
From the Department of Radiology, Oregon Health & Science University, Portland, OR. Address correspondence to Maureen S. Filipek, MD, Oregon Health & Science University, Department of Radiology, Mail Code: L340, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098. Fax: (503) 494-4982. © 2004 Elsevier Inc. All rights reserved. 0887-2171/04/2502-0002$30.00/0 doi:10.1053/j.sult.2003.12.003
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Fig 1. Acute pulmonary emboli involving both central arteries (arrows). This examination was performed on a singlearray helical CT scanner with 3-mm collimation. Note the proximal right lower lobe pulmonary arterial enlargement, consistent with an acute embolus.
increase the radiation dose by ⬎30% over the SDCT, but is roughly equivalent to the 4-detector scanners. The increase in detector number is not directly related to increase in radiation since the Z-dose radiation efficiency is better with the 16 MDCT than with the 4 MDCT.3 POSTPROCESSING TECHNIQUES
Graphics-based software advances have allowed postscan processing, with creation of thinner slice reconstructions from the raw data and improved 3-dimensional (3D) renderings. Instantaneous multiplanar reformatting techniques generated from MDCT axial cuts are leading to some of the most practical and exciting applications in thoracic imaging, particularly in evaluation of the pulmonary vasculature. This topic was thoroughly discussed in the recent literature.4-7 Four different forms of postprocessing techniques are commonly used today, each with advantages and pitfalls. Two-dimensional multiplanar reconstructions (MPR) with curved reformations can be performed quickly on workstations or on most PACS stations. MPR results in coronal and sagittal reformations that help define the craniocaudad extent of disease and better define regions of stenosis or embolization. Oblique and curvilinear views are also possible (Fig 2). Maximum intensity projections (MIPs) select out data in a given Hounsfield unit (HU) attenua-
Fig 2. Superior vena cava and pulmonary artery thrombus. (A) Right pulmonary artery embolus is evident (small arrow), along with left lower lobe atelectasis from mucus plugging. The SVC has a persistent filling defect (large arrow) that, at the time of examination, did not change from image to image, suggesting thrombus. (B) Coronal reformations confirm the presence of SVC thrombus (arrow) and demonstrate its craniocaudad extent. The thrombus originated in the left subclavian vein (not shown here).
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tion range and discard the data outside of the range. MIP is particularly helpful in displaying small volumes to further define anatomic relationships. Misrepresentation (under- and overrepresentation) errors occur more frequently with this application, especially in regions of superimposing structures (Fig 3). 3D shaded surface display (SSD) rendering techniques can create images of the vessels by choosing an HU range of the contrast medium. However, if this range is inaccurate, artificial narrowing or minimization of a stenosis can occur. Stairstep artifacts occur with this postprocessing technique, but are less of a problem with the improved z-axis coverage and thinner collimation achieved with MDCT. SSD remains a useful postprocessing method for osseous evaluation, but is not often utilized for the pulmonary vessels (Fig 4). 3D volume rendered images are the most reliable of the postprocessing techniques for vascular structures. This method uses all the data in creating final images, and is therefore more accurate (less user dependent), and has essentially replaced the
Fig 4. Shaded surface display of a patient’s ribs and scapula. Fractures are present in the left 4th through 9th ribs (arrows). This 3D representation is easy to perform, but currently has limitations with vascular imaging, and has been replaced by MIP and volume rendering techniques.
SSD. 3D volume rendering can change the shading characteristics of structures, which allows “fly through” endoluminal imaging capability. Any imaging plane can be viewed on the workstation. The thoracic anatomy can be reconstructed into a number of different presentations to highlight a particular abnormality (Fig 5). ACUTE PULMONARY ARTERIAL THROMBOEMBOLIC DISEASE
Fig 3. Incidental diagnosis of patent ductus arteriosis. A 4-mm MIP reformation of the thoracic aorta shows a small patent ductus arterosis. MIP images can “summarize” information from numerous axial scans.
Pulmonary embolus (PE) is a common event in the hospital setting. It occurs from central migration of a clot formed in the deep venous structures of the legs, pelvis, or abdomen. Deep vein thrombosis most commonly occurs secondary to prolonged stasis, trauma, or underlying hypercoaguable state. Diagnosis of PE is imperative, since undiagnosed PE is associated with high mortality.8,9 Excluding PE is also important, because long-term anticoagulation can result in serious bleeding complications.
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Fig 5. Volume rendering. (A) Severe mosaic perfusion is demonstrated with volume rendering of the lungs. The brighter areas representing increased blood flow. Of interest, this pattern matched the perfusion scan performed by nuclear medicine the previous day (not shown). (B) Volume rendering of the patient in Figure 3, demonstrating the patent ductus arteriosis (arrow). (Color version of figure is available online.)
Historically, nuclear medicine ventilation-perfusion (V/Q) scintigraphy, leg vein ultrasound, and pulmonary angiography were the mainstay for evaluating pulmonary embolus. The largest prob-
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lem with V/Q scans is the majority of patients studied (40-60%) fall into an intermediate/indeterminate probability scan (nondiagnostic), with fewer falling in a more definitive high or low probability category. V/Q scans can aid in diagnosis only when they are normal (4-40%) or high probability (10-20%).10-13 Lower extremity venous ultrasound for deep vein thrombosis is noninvasive and relatively inexpensive. However, less than half of the patients with angiographically proven PE have a positive exam.14 This means that patients with a high clinical suspicion for PE, with a nondiagnostic V/Q scan and a negative venous leg ultrasound, still require additional diagnostic studies. Even patients with a low clinical suspicion of embolus and a high probability V/Q scan require further evaluation, since only about 55% of these patients have a proven embolus by angiography.11 Prior to CTA, pulmonary angiography was the only examination that directly visualized the pulmonary arteries. The invasiveness and cost of this method are undesirable, as reflected in the practice patterns of clinicians, who rarely ordered the examination despite nondiagnostic V/Q scans.15 Additionally, studies have also shown limitations of pulmonary angiograms in the assessment of the subsegmental arterial branches.16 The PIOPED study demonstrated 66% interobserver variability in diagnosis of subsegmental thrombus, suggesting a number of these small emboli were missed. The significance of these small emboli is controversial, since a “negative” angiogram had excellent results, with only 1.7% subsequent embolic events over 6 months.17 One-year follow-up on negative CTAs has shown a similar low rate of embolic events (2%).18 With the development of single-slice spiral CT came the first opportunity to image the central and segmental pulmonary arteries within the 40-s duration of a peripheral IV contrast injection. Perhaps more importantly, in addition to assessing the pulmonary vasculature, CT offered complete evaluation of the lung parenchyma, which has led to an alternate intrathoracic diagnosis in as many as 30-60% of those studied for PE.12,19 The development of 4-row multislice scanners and 16-row multislice scanners has allowed even thinner section collimation to be used, providing improved images of subsegmental, and even 5th order, pulmonary arteries with increased sensitivity and specificity. Ghaye and colleagues20 showed that
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Fig 6. Improved visualization of an acute left lower lobe subsegmental embolus with increasingly narrow collimation. (A) 5-mm collimation, (B) 3-mm collimation, and (C) 1.5-mm collimation. As the collimation narrows, there is decreasing partial volume and improved z-axis resolution.
using 1-mm-thick reconstructed scans, 98% of subsegmental arteries are adequately analyzed, as are 74% of 5th order pulmonary arteries (Fig 6). Pulmonary CTA is now unequivocally superior to V/Q imaging in the diagnosis of pulmonary embolus, especially in patients with abnormal chest radiographs. A 1997 prospective study comparing V/Q scans with CTA showed spiral CTA to have a sensitivity of 87% and specificity of 98% in the diagnosis of acute PE compared with a sensitivity of 41%, and a specificity of 52% for a high-probability V/Q scan.10,21 This undoubtedly underestimates current sensitivity and specificity of CTA, given the technological progression of CTA resolution (MDCT) in the 5 years since this study. The limited imaging quality with thin-collimation, single-detector CT created controversy regarding the accuracy of pulmonary CTA versus pulmonary angiography.22 The sensitivity of single-detector pulmonary CTA for detection of PE has ranged widely in literature reports (between
Fig 7. The 2-mm collimation on this examination demonstrates an axial right upper lobe apical subsegmental acute embolus (arrow). Subsegmental and axial vessels are more consistently seen with the improved z-axis coverage.
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due to respiratory artifacts associated with severe dyspnea. MDCT IMAGING OF ACUTE THROMBOEMBOLIC DISEASE
Utilizing mediastinal (soft tissue) windows, pulmonary arterial filling defects are seen in acute pulmonary embolus. These may be central, marginal, or complete. Acute or subacute central filling defects form an acute angle with the vessel wall, which has been shown to be the most reliable indicator of pulmonary embolus.24 Confirming that the filling defect is arterial (versus venous) can be easily accomplished by switching to lung windows to demonstrate the accompanying bronchus or by
Fig 8. Chronic PE findings. (A) Bilateral proximal lower lobe arterial webs (arrows) from recurrent embolic events 1 year ago. (B) Right lower lobe web with calcification (arrow).
80% and 100%). The range likely reflects the evolution of CTA techniques in the past 10 years. In 2000, double-array CTA was compared to conventional angiography in a prospective study of 157 patients.23 There was no significant difference in the rate of suboptimal studies between dual-slice CT (7%) and selective pulmonary angiography (6%). Compared to selective pulmonary angiography, dual-array CT demonstrated 94% specificity and 90% sensitivity. Additionally, more central and subsegmental emboli were found by CTA than with conventional angiography (Fig 7). Past investigators have reported a 2-4% suboptimal study rate with CTA for acute PE.5 This figure is comparable to the 3% suboptimal rate of pulmonary angiography reported in the PIOPED trial.11 Suboptimal examinations are most often
Fig 9. Chronic PE findings. (A) A distal left main PA mural thrombus is present (arrow), with associated pulmonary arterial enlargement and hypertension. Note the irregular inner border of the thrombus, which distinguishes it from a lymph node. (B) The lungs demonstrate mosaic perfusion from the chronic thromboembolic disease and hypertension. Note the enlarged and more numerous pulmonary vessels in the higher density areas.
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ated calcification. Rarely, pulmonary arterial dissection has been shown to occur. As opposed to acute emboli, chronic emboli show no expansion of the vessels. The involved peripheral vessels attenuate, taper, or develop stenosis.25 Centrally, PAH is often seen and is further described below. High-resolution lung parenchymal findings of chronic pulmonary embolic disease include mosaic lung attenuation. Mosaic attenuation shows geographic regions of higher attenuation with scattered lucent regions. The higher attenuation regions have normal perfusion and the lucent (abnormal) regions have decreased perfusion with attenuation of both vessel size and number26 (Fig 9). PULMONARY MDCTA PITFALLS
False negative examinations are variable, but well known in the literature with SDCT. The rate is
Fig 10. Breathing artifact. (A) The right and left upper lobe segmental vessels demonstrate apparent partial filling defects, thought to represent emboli. (B) The lung windows at this same image show moderate respiratory motion. A repeat examination involving this region of the lung was performed before the patient left the table. These vessels were clear of emboli and therefore the filling defects were secondary to motion-related partial volume artifacts.
following the course of the vessel. Expansion of the vessel in acute emboli is a common and important ancillary finding (Fig 1). Nonopacified vessels without expansion are nondiagnostic, just as with angiography. Lung parenchymal findings of PE include wedge shaped, peripheral consolidation, representing an area of hemorrhage or possibly infarct. CHRONIC THROMBOEMBOLIC DISEASE
Chronic thromboembolic disease has several characteristic features. Mature emboli often form webs, stenosis, or areas of recanalization within the pulmonary artery (Fig 8). Mural thrombus is often seen adherent to the wall, with occasional associ-
Fig 11. Sharp algorithm artifact. (A) CTA reconstructed with a sharp algorithm demonstrates multiple low-density central filling “defects” involving all vessels within the lower lobes. Both arteries and veins are involved. The decrease in density is not as low as expected for emboli, with the exception of the right lower lobe posterior segmental branch. (B) The same image with a soft algorithm shows the right lower lobe posterior segmental embolus (arrow). The remainder of the low-density central “defects” were related to an artifact from the sharp algorithm.
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results in apparent termination of vessels or volume averaging with adjacent lung, mimicking filling defects. This artifact should be suspected by appreciating the same vascular image degradation throughout all the vessels on the same image. Viewing the same slice in lung windows will demonstrate the concurrent parenchymal motion and blurring (Fig 10). Bolus delay time is crucial for proper opacification of the arteries needed for identifying filling defect. The scan delay must be optimized for contrast arrival at the target vessels. Bolus timing depends on the cardiac output. Acquiring the images too early in the bolus results in inadequate vessel enhancement and a decreased ability to differentiate clot from surrounding blood. Imaging of the bolus too late may lead to inadequate vessel contrast enhancement toward the end of the examination.28 Reviewing CTA in a sharp (lung) algorithm results in an artificial central low density within vessels, which may lead to a false diagnosis of PE. This artifact can be recognized, since it appears at the same level throughout all the
Fig 12. Nodal tissue versus thrombus. (A) Lymph nodal tissue located at the bifurcation of left main pulmonary artery. Note the smooth inner border, which helps distinguish it from a small mural thrombus. (B) Chronic right pulmonary artery mural thrombus, which has a smooth outer border.
less with MDCT, given the increased speed and thinner collimation of this method. Though there has been little written about the actual false positive rate with SDCT or MDCT, there are numerous potential pitfalls described in the literature that result in an indeterminate scan, or possibly a false positive exam.19,27 Pitfalls can be classified as technical, physiologic, or anatomic in nature. An understanding of these interpretive pitfalls is vital for the radiologist to recognize pulmonary embolus mimics, and to reduce the false positive rate. Technical pitfalls include respiratory motion artifact, improper bolus delay, and reviewing images in a sharp algorithm. Respiratory motion artifact
Fig 13. Mucus-filled bronchus. (A) In the right lower lobe, a low-density mucus plug (arrow) is seen adjacent to the posterior segmental artery. (B) This was confirmed on the lung windows, which demonstrate multiple areas of mucus plugging and concurrent thickening of the airways.
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Fig 14. Inspiration-associated interruption of contrast. (A) The initial images at the base of the heart and lower lobe vessels demonstrate opacification of the right ventricle and pulmonary arteries. These images were obtained immediately after deep inspiration. (B) Unopacified blood enters from the IVC, diluting the contrast column within the right heart. Normal opacification is present in the left ventricle and pulmonary veins. (C) Severe decrease in density is present involving the right ventricle and pulmonary arteries, leading to a false positive diagnosis of pulmonary embolus. (D) Images at the level of the main pulmonary artery show return of the normal opacification. This interruption of the contrast bolus is a common finding, though usually it is milder in severity.
arteries, and often the veins as well. The relative decrease in density is not as severe as that seen with embolic defects and there is no vascular expansion. The central low density is thought to result from a sharpening artifact, potentially from laminar flow. To avoid this artifact, all vascular evaluation should be conducted in a soft tissue algorithm. Figure 11 compares the appearance of the pulmonary arteries in sharp and soft algorithms. Streak artifact and beam hardening around the superior vena cava can also mimic thrombus within the apical segment of the right upper lobe
artery and main right pulmonary artery, creating diagnostic problems in these areas. Some authors have advocated the use of a postcontrast saline flush to dilute the end of the bolus and reduce this artifact.29 Normal anatomic structures, such as veins, lymph nodes, axial vessels, and mucus plugging, can mimic PE. Intrapulmonary lymph nodes are not usually rounded in shape, but usually are more elongated and flat in appearance. Knowledge of the size and location of pulmonary hilar lymph nodes is crucial, because they are seen as low-density structures adjacent to vessels and may mimic in-
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Table 1. Clinical Classification of Pulmonary Hypertension* 1. Precapillary pulmonary arterial hypertension (a) Primary pulmonary hypertension Sporadic Familial (b) Related to Collagen vascular disease Congenital systemic to pulmonary shunts Portal hypertension HIV infection Drugs/toxigens (anorexigens and others) Persistent pulmonary hypertension of the newborn 2. Pulmonary venous hypertension (a) Left-sided atrial or ventricular heart disease (b) Left-sided valvular disease (c) Pulmonary veno-occlusive disease (d) Extrinsic compression of central pulmonary veins Fibrosing mediastinitis Adenopathy/tumor 3. Disorders of the respiratory system and/or hypoxemia (a) Chronic obstructive pulmonary disease (b) Interstitial lung disease (c) Sleep disordered breathing (d) Alveolar hypoventilation disorders (e) Chronic high altitude exposure (f) Neonatal lung disease (g) Alveolar-capillary dysplasia 4. Pulmonary hypertension due to chronic thrombotic and/or embolic disease (a) Thromboembolic obstruction of proximal pulmonary arteries (b) Obstruction of distal pulmonary arteries Pulmonary embolism (thrombus, tumor, ova and/or parasites, foreign material In situ thrombosis Sickle cell disease 5. Pulmonary hypertension due to disorders directly affecting the pulmonary vasculature (a) Inflammatory Schistosomiasis Sarcoidosis (b) Pulmonary capillary hemangiomatosis *From the 1998 World Symposium on Primary Pulmonary Hypertension.35
traluminal marginal filling defects, especially at vessel bifurcations. Lymph nodes can be differentiated from mural thickening (chronic PE), since the lymph nodes have a smooth inner border while chronic thrombus has a smooth outer border, as seen in Figure 12. Mucus plugging is a common abnormality, and is a well-described diagnostic pitfall occasionally leading to misdiagnosis of PE. Mucus plugging can be recognized by identifying an enhancing vessel next to the filled bronchus and by the absence of a lucent airway on lung windows (Fig 13). Multiplanar reformations also can aid in the anatomical discrimination of the bronchus and artery. There are also physiological circumstances that can lead to a false diagnosis of emboli.30,31 Patent foramen ovale or atrial septal defect may permit opacified blood to escape from the right atrium into the systemic circulation, decreasing the contrast level in the pulmonary arteries to nondiagnostic levels. Such intracardiac shunts are indicated by initial high level of opacification of the aorta, possibly exceeding that of the pulmonary artery. A second physiologic problem is transient interruption of the contrast column occurring with deep inspiration at the beginning of the examination, which causes the inflow of unopacified blood into the right heart chambers from the IVC.28,30,31 Inflow of unopacified blood generally occurs in patients with normal right heart pressures and appears as a short, uniform decrease in arterial opacification, without vascular expansion (Fig 14). Characteristically, this contrast defect is observed in all pulmonary arteries at the same level. Another important clue is the presence of decreased opacification within the right heart chambers just before the contrast deficit occurs within the pulmonary arteries.
Table 2. Causative Physiologic Alterations for Developing Pulmonary Arterial Hypertension Physiologic Etiology for PAH
Increased flow Chronic hypoxia Vessel obliteration Chronic pulmonary venous hypertension
Examples
Atrial septal defect, ventricular septal defect, transposition of great vessels, common atrio/ventricular canal, partial anomolous venous return Chronic bronchitis, bronchiolitis obliterans, advanced pulmonary fibrosis, sleep apnea, cystic fibrosis, chronic high altitude exposure Emphysema, primary pulmonary hypertension, chronic thromobembolic disease, vasculitis, sickle-cell disease, schistosomiasis, tumor emboli Left ventricular or atrial disease, left-sided valvular disease, pulmonary venoocclusive disease, and capillary hemangiomatosis
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1. primary pulmonary hypertension, 2. pulmonary venous hypertension, 3. pulmonary hypertension associated with disorders of the respiratory system and/or hypoxemia, 4. pulmonary hypertension due to thromboembolic disease, and
Fig 15. Enlargement of the main pulmonary artery is defined as greater than the ascending aorta, as clearly seen here, or >29 mm. A small amount of mural thrombus is seen along the left distal main pulmonary artery (arrow).
PULMONARY ARTERIAL HYPERTENSION
Normal pulmonary arteries have three layers, ie, a single layer of endothelial cells, a medial smooth muscle layer, and an outer adventitial layer. The large elastic arteries have diameters greater than 0.5 mm and accompany an adjacent bronchiole to the subsegmental level. Distal to this, they transition to muscular arteries, which accompany the terminal bronchioles. As the artery travels peripherally it becomes an arteriole with a thinner smooth muscle layer. The arteriole caliper further diminishes and continues with the respiratory bronchiole to form a terminal capillary network in the alveolar walls. PAH, regardless of cause, is a severe disease with a dismal natural outcome. The symptoms of pulmonary hypertension can be illusive and nonspecific (dyspnea and fatigue) and this frequently delays diagnosis until the disease is advanced.32 Current therapies for PAH are limited, and include lung transplantation and intravenous prostacyclin (arterial dilator).33 PAH is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest as determined with right heart catheterization. (Normal pulmonary arterial wedge pressure is ⬍12 mmHg.32) Pulmonary hypertension secondary to known cardiac, pulmonary, or hepatic disease is far more common than primary pulmonary hypertension where there is no identifiable cause. The World Health Organization has classified PAH into the following five types:34
Fig 16. (A) Right ventricular hypertrophy. The thickness of the right ventricular wall (arrows) is excessive. Normally the wall thickness should not exceed 4 mm. The interventricular septum does not demonstrate the normal mild bowing toward the right ventricular chamber. Mild dilation of the right atrium and IVC is also present. (B) Coronal reformation demonstrates chronic thromboembolic disease (arrows) along with reflux of contrast into the IVC and hepatic veins.
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5. pulmonary hypertension due to disorders directly affecting the pulmonary vasculature (Table 1). Others have described pulmonary hypertension by the location of the defect or process relative to the capillary bed (precapillary, capillary, and postcapillary).35 We find it practical to categorize PAH etiology by four basic underlying physiologic alterations that represent the most common causes for pulmonary hypertension: increased flow (left to right shunt), chronic hypoxia, vessel obliteration, and chronic pulmonary venous hypertension (Table 2). PRIMARY AND SECONDARY PAH IMAGING FINDINGS
MDCT has a primary role in diagnosing PAH and identifying possible causes. MDCT can discriminate a primary lung parenchymal disease (fibrosis or small airways disease) or a primary cardiac process (septal defects, valvular disease, or myocardial failure) as the main contributing factor to PAH, as opposed to an intrinsic pulmonary vascular disease. MDCT imaging can concurrently assess the state of the right ventricle and assess for cor pulmonale. It is important, when possible, to identify chronic pulmonary venous hypertension as the predominant physiological etiology of PAH, as treating postcapillary processes with prostacyclin can result in a deleterious outcome from worsened or fatal pulmonary edema.33 Tan et al36 concluded, in their retrospective study, that a main pulmonary artery diameter of 29 mm or greater identifies patients with even mild PAH. Others have described a larger transverse pulmonary artery diameter than the adjacent ascending aorta as evidence of PAH (Fig 15). Measurement of the right and left intrapericardial portions of the pulmonary arteries has also been described in evaluating PAH. They are considered enlarged if their diameter is ⬎18 mm at 1-cm distance from their origin.37 Enlargement of the lobar arteries to a greater diameter than the accompanying bronchus is also a useful sign (for conventional radiographs as well). Right heart disease is a common and expected secondary finding of PAH due to the increased workload of the right heart. The increased pressure transferred to the right heart results in right-sided enlargement and hypertrophy. Right atrial enlargement is defined as ⬎35 mm in transverse diameter, and right ventricle enlargement is defined as ⬎45
mm in transverse diameter.33,37 At times, the elevated right ventricular pressures (end diastolic pressure) is severe enough to cause bowing of the interventricular septum toward the left ventricle38 (Fig 16). The inferior vena cava is also frequently dilated. Elevated end diastolic right heart pressures can be hemodynamically observed through contrast bolus dynamics. Elevated right heart pressures cause reflux of hyperdense contrast into the IVC and the hepatic veins28 (Fig 17). Constrictive pericarditis and right heart failure (with normal pulmonary arteries) can also demonstrate IVC reflux and must be excluded as a cause. When there is clinical or radiographic evidence of elevated right heart pressures, it is prudent to perform a CT timing bolus, since pulmonary artery opacification may be quite delayed by decreased right ventricular outflow. The absence of venous reflux, or the presence of unopacified mixing in the right heart chambers from a decompressed IVC, argues against any significant elevation of right heart pressures and concurrently the presence of PAH. Assessing the diameter and distribution of the pulmonary veins/venous flow aids in diagnosing postcapillary pulmonary hypertension. Enlarged pulmonary veins and cephalization indicate chronic pulmonary venous hypertension secondary to left-sided heart disease, often with concurrent dilation of left heart chambers. Septal thickening is an occasional concurrent imaging manifestation in chronic venous hypertension39 (Fig 18).
Fig 17. Hyperdense reflux of contrast into the dilated IVC and hepatic veins. This contrast flow is often seen in patients with elevated right atrial and ventricular pressures. In this case, the patient had markedly elevated pulmonary artery pressures.
MULTIDETECTOR PULMONARY CT ANGIOGRAPHY
UNUSUAL CAUSES OF PULMONARY ARTERIAL HYPERTENSION
Pulmonary veno-occlusive disease is an uncommon disorder, which is caused by the gradual obliteration of pulmonary veins. Intimal proliferation and fibrosis of the veins are found on pathology. The chronic elevation of the venous pressures eventually leads to PAH. Multiple etiologies are associated with this pathological process. The prognosis is poor, with progression of symptoms and death often over a few years. The most common MDCT findings are ground glass opacification, interlobular septal thickening, pleural and pericardial effusion, and no enlargement of left
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heart chambers (Fig 18). This latter finding helps distinguish pulmonary veno-occlusive disease from the more common cardiac causes of pulmonary venous hypertension.5,33,40 Pulmonary capillary hemangiomatosis is a rare cause of PAH, representing the proliferation of thin-walled capillary-like vessels, which invade the veins and arterioles. It is associated with intimal fibrosis, hemorrhage, and venous stenosis. The etiology is unknown, but it may represent a form of low-grade malignancy or metastatic dissemination of an angiosarcoma. MDCT imaging, clinical course, and prognosis are similar to pulmonary veno-occlusive disease.5,33,40
Fig 18. Pulmonary veno-occlusive disease. A 55-year-old male with progressive worsening dyspnea and recurrent episodes of “heart failure.” (A) Enlarged pulmonary artery, consistent with hypertension. (B) Right ventricular hypertrophy and a straightened interventricular septum. However, the left ventricle does not demonstrate any dilation or hypertrophy. (C) Bilateral ground glass opacity and septal thickening. This latter finding is consistent with a postcapillary pathology, but the normal appearing left ventricle and left atrium (not shown) suggest that the problem is not cardiac. Open lung biopsy demonstrated pulmonary veno-occlusive disease.
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Fig 19. Arterial tumor embolization. A 48-year-old male with progressive dyspnea over the last 4 weeks. (A) Widespread “tree-in-bud” opacities are present, suggestive of an active inflammatory process in the bronchioles. (B) Expiratory images did not show any air trapping, which is not consistent with small airways disease (ie, respiratory bronchial inflammation). (C) Contrast-enhanced image though the heart demonstrates a large mass arising in the right atrium and ventricle. Open lung biopsy showed numerous tumor emboli and lymphangitic spread of tumor along the distal arteries from the patient’s cardiac angiosarcoma.
Pulmonary arterial tumor embolism often presents with progressive dyspnea due to PAH. It is a difficult diagnosis to make clinically, requiring a high clinical suspicion. Intravascular embolic disease on MDCT is usually manifested with numerous branching vascular “tree-in-bud” opacities with a beaded appearance (Fig 19). Peripheral areas of infarction have been described.41 The importance of expiratory images has not been emphasized in these rare cases. The presence of treein-bud opacities usually is secondary to filling of the terminal bronchioles with an active inflammatory process. Focal air trapping is often seen in the
areas of greatest involvement. Absence of airtrapping should suggest that the tree-in-bud opacities may not be located within the terminal bronchioles, and other diseases, such as tumor emboli, should be considered. CONCLUSION
The evaluation of pulmonary embolus and pulmonary arterial hypertension is greatly expanding application of MDCT. The improved contrast-enhanced imaging is allowing for more refined diagnoses and characterization of PAH and thromboembolic disease. This article and recent similar
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publications aim to increase insight and knowledge of this rapidly progressing modality. The radiologist’s knowledge of appropriate pulmonary MDCT
use, pulmonary MDCTA pitfalls, contrast dynamics, and high-resolution anatomy is essential for optimal image interpretation.
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