Imaging of Acute and Chronic Thromboembolic Disease: State of the Art PDF 2017

Clinical Radiology 72 (2017) 375e388 Contents lists available at ScienceDirect Clinical Radiology journal homepage: www.clinicalr...

Clinical Radiology 72 (2017) 375e388 Contents lists available at ScienceDirect Clinical Radiology journal homepage: www.clinicalradiologyonline.net Review Imaging of acute and chronic thromboembolic disease: state of the art A. Ruggiero, N.J. Screaton* Department of Radiology, Papworth Hospital, Cambridge, UK art icl e i nformat ion Acute pulmonary embolism (PE) is a life-threatening condition that requires prompt diagnosis Article history: and treatment. Recent advances in imaging allow acute and rapid recognition even by the non- Received in revised form specialist radiologist. Most acute emboli resolve on anticoagulation without sequelae; how- 23 January 2017 ever, some emboli fail to fully resolve becoming endothelialised with the development of chronic thromboembolic disease (CTED). Increased pulmonary vascular resistance arising from CTED may lead to chronic thromboembolic pulmonary hypertension (CTEPH) a debilitating disease affecting up to 5% of survivors of acute PE. Diagnostic evaluation is more complex in CTEPH/CTED than acute PE with subtle imaging features often being overlooked or mis- interpreted. Differentiation of acute from chronic PE and from other forms of pulmonary hy- pertension has profound therapeutic implications. Diverse imaging techniques are available to diagnose and monitor PEs both in the acute and chronic setting. Broadly they include tech- niques that provide data on lung parenchymal perfusion (ventilationeperfusion [VQ] scin- tigraphy), angiographic techniques (computed tomography [CT], magnetic resonance imaging [MRI], and invasive angiography) or a combination of both (MR angiography and time-resolved angiography or dual-energy CT angiography). This review aims to describe state of the art imaging highlighting the strength and weaknesses of individual techniques in the diagnosis of acute and chronic PE. Crown Copyright Ó 2017 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved. Introduction unnecessary treatment is associated with significant morbidity. Acute pulmonary embolism An overall annual incidence of 100e200 per 100,000 inhabitants for both DVT and acute PE has been reported2,3; Pulmonary embolism (PE) is the third most common however, the epidemiology of acute PE is rather difficult to acute cardiovascular disease after coronary artery disease determine as it may remain asymptomatic (in more than and stroke.1 PE typically results from migration of deep vein two-thirds of patients)4,5 or it is an incidental finding, thrombosis (DVT) from the lower limb. Rapid and accurate sometimes its first presentation can be sudden cardiac diagnosis is crucial as untreated outcomes are poor and death. Clinical signs and symptoms of acute PE are non- specific with imaging being key to establishing the diagnosis. Massive PE is characterised by systemic hypotension * Guarantor and correspondent: N. J. Screaton, Department of Radiology, Papworth Hospital, Cambridge, UK. Tel.: þ44 01480 364436. (systolic arterial pressure 50 years has been proposed with a fivefold increase in the proportion of pa- Chronic thromboembolic disease tients in whom PE could be ruled out without further im- aging10; however, D-dimer is less useful in patients already Incomplete resolution and recanalisation of acute emboli hospitalised as its values can be raised in pneumonia, results in chronic thromboembolic disease (CTED) with myocardial infarction, sepsis, cancer, pregnancy, and in the organisation and endothelialisation of thromboembolic postoperative state. material and formation of laminated thrombi, single bands Although the ECG can be normal in patients with massive parallel to the vessel (shelves) or multiple bands in a com- or sub-massive it may show typical features such as inver- plex web-like network as well as complete vascular occlu- ted T waves in the precordial leads,11 right bundle branch sions. The pathophysiological basis underpinning the block and the classic S1Q3T3 pattern suggestive of right transition from acute to chronic thromboembolism is un- heart strain. The chest radiograph is performed to identify certain; however, failed thrombolysis, a localised inflam- mimics of PE such as pneumonia, pneumothorax, or matory response and localised endothelial dysfunction, congestive cardiac failure and can be normal in patients may be responsible.20 CTED can occur without or with with massive PE. Ninety percent of PE arise from DVT in a chronic thromboembolic pulmonary hypertension (CTEPH). lower limb12 with venous compression ultrasound (VCU) The evolution from acute PE to CTED and CTEPH is carrying both a high sensitivity (>90%) and specificity (95%) incompletely understood, it may result from a single pul- for symptomatic DVT.2,13 Therefore, if clinical and D-dimer monary embolic event or recurrent PEs.21 Patients with evaluation is suggestive of PE in patients with signs and CTEPH often witness an initial “honeymoon period” with symptoms of DVT VCU is indicated. This is of particular improvement in symptoms following acute PE, which is value in the pregnant patient with suspected PE as it avoids followed by an insidious onset of progressive dyspnoea, the need for ionising radiation. The utility of VCU screening chest pain, and right heart failure; however, not all patients in patients with suspected DVT but no symptoms of DVT is who develop CTEPH describe prior VTE episodes. Interna- controversial.14 In the context of suspected PE, VCU can be tional registry data confirmed prior observations and re- limited to the assessment of the deep veins from the groin ported a history of acute PE in 74.8% and DVT in 56.1% of to the popliteal fossa. The VCU diagnosis of DVT in patients CTEPH patients.22 Therefore, the absence of a previous acute suspected of having PE is considered sufficient to start thromboembolic event does not exclude CTEPH. The cu- anticoagulant treatment without additional testing.15 mulative incidence of CTEPH following PE is 1.3e5.1% after 1 Anticoagulant treatment alone is recommended over year23,24 and 0.8e3.8 after 2 years.25,26 This rather high thrombolytic therapy in the majority of patients with acute margin of error is likely related to referral bias, absence of DVT. The assessment of mortality risk in patients with acute early symptoms, and the difficulty in differentiating “true” PE is used to define the treatment approach.2 High-risk PE is acute PE from an acute episode of PE on pre-existing characterised by overt haemodynamic compromise (systolic CTEPH.2 Clinically, CTEPH is defined as mean pulmonary blood pressure 1:1 in three or four lobes in the presence of a dilated (29 mm)  A. Ruggiero, N.J. Screaton / Clinical Radiology 72 (2017) 375e388 385 Figure 9 (a) RV enlargement (ratio of the RVeLV diameters >1:1) with straightening of the interventricular septum (b) diastolic leftward motion of the interventricular septum to cause the deformation of the LV, “D shape”, as a result of the pressure differential between LV and RV chambers. (c) Late gadolinium enhancement at the inferior insertion point of the inter-ventricular septum, which is related to the mechanical strain caused by elevated RV pressure and is a negative prognostic indicator. main pulmonary artery and absence of significant structural MR demonstrates this dynamic diastolic leftward motion lung disease has a specificity of 100% for the presence of of the interventricular septum to cause the deformation of pulmonary hypertension89,90 but this sign is less reliable in the LV, “D shape”, as a result of the pressure differential CTEPH due to distal attenuation of obstructed vessels. In between left and RV chambers. Beyar et al demonstrated in CTEPH the bronchial circulation may appear markedly an animal model that interventricular septal bowing is increased due to increased systemic-to-pulmonary shunts present when the pressure differential between the right which help to maintain pulmonary blood flow (Fig 8). and left ventricle exceeds 5 mmHg and a strong association The imaging appearances of CTED are similar in CTPA and between inter-ventricular septal curvature and the RVeLV in MRPA, but laminated thrombus detection is more diffi- pressure gradient was demonstrated as RV pressure cult in MRPA. The sensitivity of MRPA is lower than that of increases.96 digital subtraction angiography or CTPA for detection of Dilatation of the tricuspid valve annulus secondary to RV subsegmental webs and bands. The main strength of MRPA enlargement results in a degree of tricuspid regurgitation is related to the fact that it does not require the use of which can be manifest on CT as a column of contrast ionising radiation or iodinated contrast medium.91 Overall, retrograde filling the inferior vena cava and the hepatic CTPA remains superior because of the ease of use, short veins (though at high injection rates a degree of inferior acquisition time and high spatial resolution.92,93 In CTEPH vena cava filling may be normal). MRI is helpful to visualise abnormally enlarged bronchial and non-bronchial (inter- the tricuspid regurgitation and quantitatively characterise costal arteries, internal mammary arteries, inferior phrenic this finding. arteries) which are frequently present can account for 30% Slightly enlarged thoracic lymph nodes have also been of systemic blood flow.94 CTPA provides a more accurate described in association with CTPEH97 correlating histo- assessment of these collaterals vessels than DSPA or MRPA logically with vascular transformation of the sinus with a but requires simultaneous opacification of the pulmonary degree of sclerosis. and systemic circulation. Usually reformatted multiplanar images and volume rendering technique allow a better Parenchymal features understanding of the origin and course of the collateral A mosaic perfusion pattern reflects reduced perfusion in vessels. MR allows to quantify the systemic to pulmonary areas subtended by occluded or stenosed vessels. It appears collateral flow.95 on CT as sharply demarcated areas of low attenuation with small vascular calibre contrasting with areas of increased Indirect (cardiac) features attenuation with larger vessels representing the normal/ Increased pulmonary pressures result in RV hypertrophy hyper-perfused lung. characterised by free wall thickness >4 mm (Fig 8). Over The mosaic pattern is non-specific as it can be seen in time RV function deteriorates resulting in RV enlargement CTEPH as well as in small airway disease. Classically, in defined as the ratio of the RVeLV diameters >1:1. patients with CTEPH there is a well-demarcated segmental Straightening and often right-to-left bowing of the inter- or subsegmental distribution of the mosaicism due to the ventricular septum is characteristic of right heart strain vascular distribution of the thromboemboli. In small air- (Fig 9). ways disease the mosaic pattern has a more patchy 386 A. Ruggiero, N.J. Screaton / Clinical Radiology 72 (2017) 375e388 pattern (Fig 10). Wedge unmatched perfusion defect can be demonstrated on V/QSCAN both in the acute and chronic PE. Conclusion Acute thromboembolic disease is common with diag- nostic pathways involving pretest probability assessment, D-dimer, and imaging being widely advocated by interna- tional guidelines. Chronic thromboembolic disease is increasingly recognised as a not infrequent sequela of prior acute emboli, which is often initially overlooked with considerable delay in diagnosis. Among all imaging mo- dalities, CTPA plays a key role both in the acute and chronic setting of thromboembolic disease. Although the imaging features of acute PE are easily recognised and enable prompt the appropriate treatment, features of CTED or CTEPH are more subtle and often difficult to diagnose. This review has aimed to provide an up-to-date overview of the diagnostic accuracy of all the available techniques as well as the most common appearances to help identify and describe the findings. The capabilities of dual-energy CTPA have been exploited in the past few years and further studies are required to justify its routine use in clinical practice. References 1. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet 2012;379(9828):1835e46. 2. Konstantinides SV. 2014 ESC guidelines on the diagnosis and manage- ment of acute pulmonary embolism. Eur Heart J 2014;35(45):3145e6. 3. Heit JA. The epidemiology of venous thromboembolism in the com- munity. Arterioscler Thromb Vasc Biol 2008;28(3):370e2. 4. Krutman M, Wolosker N, Kuzniec S, et al. Risk of asymptomatic pul- monary embolism in patients with deep venous thrombosis. J Vasc Surg Venous Lymphat Disord 2013;1(4):370e5. 5. Tzoran I, Saharov G, Brenner B, et al. Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs. J Thromb Haemost 2012;10(4):564e71. Figure 10 (a) Contrast-enhanced 3D MRPA showing almost complete 6. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical occlusion of the right lower lobe pulmonary artery (arrow), distal model to categorize patients probability of pulmonary embolism: perfusion defect in the right upper lobe and segmental filling defect increasing the models utility with the SimpliRED D-dimer. Thromb in the left upper lobe (b) axial image of MRPA showing areas of Haemost 2000;83(3):416e20. reduced perfusion in both upper lobes. 7. Wicki J, Perneger TV, Junod AF, et al. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 2001;161(1):92e7. distribution reflecting the air-trapping within individual 8. Wakai A. Emergency department-based atrial fibrillation treatment lobules. Similarly other features suggestive either of airways strategy with low-molecular-weight heparin. Ann Emerg Med disease (e.g., bronchiectasis) or pulmonary hypertension 2003;41(5):757e8 [author reply: 758e9]. 9. Carrier M, Righini M, Djurabi RK, et al. VIDAS D-dimer in combination (pulmonary artery/RV dilatation) need to be taken into ac- with clinical pre-test probability to rule out pulmonary embolism. A count. Patchy areas of ground-glass change can be seen at systematic review of management outcome studies. Thromb Haemost the periphery of the lung suggestive of systemic perfu- 2009;101(5):886e92. sion.62 Wedge-shaped areas of consolidation (infarction) 10. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff seen at CT in the acute setting usually resolve with small levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014;311(11):1117e24. parenchymal scars, peripheral nodules, cavities or irregular 11. Henzler T, Roeger S, Meyer M, et al. Pulmonary embolism: CT signs and peripheral lines. cardiac biomarkers for predicting right ventricular dysfunction. Eur In CTED/CTEPH MR perfusion images obtained during Respir J 2012;39(4):919e26. peak parenchymal enhancement (following injection of 12. Sevitt S, Gallagher N. Venous thrombosis and pulmonary embolism. A gadolinium) delineate single or multiple well-demarcated clinico-pathological study in injured and burned patients. Br J Surg 1961;48:475e89. areas of low signal corresponding to perfusion defects 13. Kearon C, Ginsberg JS, Hirsh J. The role of venous ultrasonography in the which can be classified as lobar, segmental, or sub- diagnosis of suspected deep venous thrombosis and pulmonary embo- segmental which constitute an MR mosaic perfusion lism. Ann Intern Med 1998;129(12):1044e9.  A. Ruggiero, N.J. Screaton / Clinical Radiology 72 (2017) 375e388 387 14. Schoepf UJ, Goldhaber SZ, Costello P. Spiral computed tomography for 39. Thieme SF, Becker CR, Hacker M, et al. Dual energy CT for the assess- acute pulmonary embolism. Circulation 2004;109(18):2160e7. ment of lung perfusiondcorrelation to scintigraphy. Eur J Radiol 15. Le Gal G, Righini M, Sanchez O, et al. A positive compression ultraso- 2008;68(3):369e74. nography of the lower limb veins is highly predictive of pulmonary 40. Thieme SF, Graute V, Nikolaou K, et al. Dual energy CT lung perfusion embolism on computed tomography in suspected patients. Thromb imagingdcorrelation with SPECT/CT. Eur J Radiol 2012;81(2):360e5. Haemost 2006;95(6):963e6. 41. Chae EJ, Seo JB, Jang YM, et al. Dual-energy CT for assessment of the 16. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE dis- severity of acute pulmonary embolism: pulmonary perfusion defect ease: CHEST guideline and expert panel report. Chest score compared with CT angiographic obstruction score and right ven- 2016;149(2):315e52. tricular/left ventricular diameter ratio. AJR Am J Roentgenol 17. Piran S, Schulman S. Management of venous thromboembolism: an 2010;194(3):604e10. update. Thromb J 2016;14(Suppl. 1):23. 42. Ikeda Y, Yoshimura N, Hori Y, et al. Analysis of decrease in lung perfusion 18. Sharifi M, Bay C, Skrocki L, et al. Moderate pulmonary embolism treated with blood volume with occlusive and non-occlusive pulmonary embolisms. thrombolysis (from the “MOPETT” Trial). Am J Cardiol 2013;111(2):273e7. Eur J Radiol 2014;83(12):2260e7. 19. Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate- 43. Hoey ET, Mirsadraee S, Pepke-Zaba J, et al. Dual-energy CT angiography risk pulmonary embolism. N Engl J Med 2014;370(15):1402e11. for assessment of regional pulmonary perfusion in patients with chronic 20. Lang IM, Pesavento R, Bonderman D, et al. Risk factors and basic thromboembolic pulmonary hypertension: initial experience. AJR Am J mechanisms of chronic thromboembolic pulmonary hypertension: a Roentgenol 2011;196(3):524e32. current understanding. Eur Respir J 2013;41(2):462e8. 44. Kim SS, Hur J, Kim YJ, et al. Dual-energy CT for differentiating acute and 21. Fedullo P, Kerr KM, Kim NH, et al. Chronic thromboembolic pulmonary chronic pulmonary thromboembolism: an initial experience. Int J Car- hypertension. Am J Respir Crit Care Med 2011;183(12):1605e13. diovasc Imaging 2014;30(Suppl. 2):113e20. 22. Pepke-Zaba J, Delcroix M, Lang I, et al. Chronic thromboembolic pul- 45. Hong YJ, Kim JY, Choe KO, et al. Different perfusion pattern between monary hypertension (CTEPH): results from an international prospec- acute and chronic pulmonary thromboembolism: evaluation with two- tive registry. Circulation 2011;124(18):1973e81. phase dual-energy perfusion CT. AJR Am J Roentgenol 23. Miniati M, Monti S, Bottai M, et al. Survival and restoration of pulmo- 2013;200(4):812e7. nary perfusion in a long-term follow-up of patients after acute pul- 46. Kluge A, Luboldt W, Bachmann G. Acute pulmonary embolism to the monary embolism. Medicine (Baltimore) 2006;85(5):253e62. subsegmental level: diagnostic accuracy of three MRI techniques 24. Ribeiro A, Lindmarker P, Johnsson H, et al. Pulmonary embolism: one- compared with 16-MDCT. AJR Am J Roentgenol 2006;187(1):W7e14. year follow-up with echocardiography Doppler and five-year survival 47. Ley S, Grunig E, Kiely DG, et al. Computed tomography and magnetic analysis. Circulation 1999;99(10):1325e30. resonance imaging of pulmonary hypertension: pulmonary vessels and 25. Becattini C, Agnelli G, Pesavento R, et al. Incidence of chronic throm- right ventricle. J Magn Reson Imaging 2010;32(6):1313e24. boembolic pulmonary hypertension after a first episode of pulmonary 48. Kreitner KF, Kunz RP, Ley S, et al. Chronic thromboembolic pulmonary embolism. Chest 2006;130(1):172e5. hypertensiondassessment by magnetic resonance imaging. Eur Radiol 26. Pengo V, Lensing AW, Prins MH, et al. Incidence of chronic thrombo- 2007;17(1):11e21. embolic pulmonary hypertension after pulmonary embolism. N Engl J 49. Kalb B, Sharma P, Tigges S, et al. MR imaging of pulmonary embolism: Med 2004;350(22):2257e64. diagnostic accuracy of contrast-enhanced 3D MR pulmonary angiog- 27. Riedel M, Stanek V, Widimsky J, et al. Long-term follow-up of patients raphy, contrast-enhanced low-flip angle 3D GRE, and nonenhanced with pulmonary thromboembolism. Late prognosis and evolution of free-induction FISP sequences. Radiology 2012;263(1):271e8. hemodynamic and respiratory data. Chest 1982;81(2):151e8. 50. Stein PD, Chenevert TL, Fowler SE, et al. gadolinium-enhanced magnetic 28. Ameli-Renani S, Rahman F, Nair A, et al. Dual-energy CT for imaging of resonance angiography for pulmonary embolism: a multicentre pro- pulmonary hypertension: challenges and opportunities. RadioGraphics spective study (PIOPED III). Ann Intern Med 2010;152(7):434e43. 2014;34(7):1769e90. W142e433. 29. Remy-Jardin M, Pistolesi M, Goodman LR, et al. Management of sus- 51. Nikolaou K, Schoenberg SO, Attenberger U, et al. Pulmonary arterial pected acute pulmonary embolism in the era of CT angiography: a hypertension: diagnosis with fast perfusion MR imaging and high- statement from the Fleischner Society. Radiology 2007;245(2):315e29. spatial-resolution MR angiographydpreliminary experience. Radiology 30. Cannon JE, Su L, Kiely DG, et al. Dynamic risk stratification of patient 2005;236(2):694e703. long-term outcome after pulmonary endarterectomy: results from the 52. Rajaram S, Swift AJ, Telfer A, et al. 3D contrast-enhanced lung perfusion United Kingdom national cohort. Circulation 2016;133(18):1761e71. MRI is an effective screening tool for chronic thromboembolic pulmo- 31. Jenkins DP, Madani M, Mayer E, et al. Surgical treatment of chronic nary hypertension: results from the ASPIRE Registry. Thorax thromboembolic pulmonary hypertension. Eur Respir J 2013;68(7):677e8. 2013;41(3):735e42. 53. Ley S, Ley-Zaporozhan J, Pitton MB, et al. Diagnostic performance of 32. Jenkins DP, Biederman A, D’Armini AM, et al. Operability assessment in state-of-the-art imaging techniques for morphological assessment of CTEPH: lessons from the CHEST-1 study. J Thorac Cardiovasc Surg vascular abnormalities in patients with chronic thromboembolic pul- 2016;152(3):669e674 e663. monary hypertension (CTEPH). Eur Radiol 2012;22(3):607e16. 33. Jenkins D. Pulmonary endarterectomy: the potentially curative treat- 54. van Langevelde K, Tan M, Sramek A, et al. Magnetic resonance imaging ment for patients with chronic thromboembolic pulmonary hyperten- and computed tomography developments in imaging of venous sion. Eur Respir Rev 2015;24(136):263e71. thromboembolism. J Magn Reson Imaging 2010;32(6):1302e12. 34. Cerveri I, D’Armini AM, Vigano M. Pulmonary thromboendarterectomy 55. Freed BH, Gomberg-Maitland M, Chandra S, et al. Late gadolinium almost 50 years after the first surgical attempts. Heart enhancement cardiovascular magnetic resonance predicts clinical 2003;89(4):369e70. worsening in patients with pulmonary hypertension. J Cardiovasc Magn 35. Wiener RS, Schwartz LM, Woloshin S. When a test is too good: how CT Reson 2012;14:11. pulmonary angiograms find pulmonary emboli that do not need to be 56. Gatehouse PD, Keegan J, Crowe LA, et al. Applications of phase-contrast found. BMJ 2013;347:f3368. flow and velocity imaging in cardiovascular MRI. Eur Radiol 36. Morley NC, Muir KC, Mirsadraee S, et al. Ten years of imaging for pul- 2005;15(10):2172e84. monary embolism: too many scans or the tip of an iceberg? Clin Radiol 57. Reiter U, Reiter G, Fuchsjager M. MR phase-contrast imaging in pul- 2015;70(12):1370e5. monary hypertension. Br J Radiol 2016;89(1063):20150995. 37. Screaton NJ, Karia S. Commentary on “Ten years of imaging for pulmo- 58. Grothues F, Moon JC, Bellenger NG, et al. Interstudy reproducibility of nary embolism: too many scans or the tip of an iceberg?”. Clin Radiol right ventricular volumes, function, and mass with cardiovascular 2015;70(12):1355e6. magnetic resonance. Am Heart J 2004;147(2):218e23. 38. Lu GM, Luo S, Meinel FG, et al. High-pitch computed tomography pul- 59. Hudson ER, Smith TP, McDermott VG, et al. Pulmonary angiography monary angiography with iterative reconstruction at 80 kVp and 20 ml performed with iopamidol: complications in 1,434 patients. Radiology contrast agent volume. Eur Radiol 2014;24(12):3260e8. 1996;198(1):61e5. 388 A. Ruggiero, N.J. Screaton / Clinical Radiology 72 (2017) 375e388 60. Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of 79. Qanadli SD, El Hajjam M, Vieillard-Baron A, et al. New CT index to pulmonary angiography in acute pulmonary embolism. Circulation quantify arterial obstruction in pulmonary embolism: comparison with 1992;85(2):462e8. angiographic index and echocardiography. AJR Am J Roentgenol 61. Diffin DC, Leyendecker JR, Johnson SP, et al. Effect of anatomic distri- 2001;176(6):1415e20. bution of pulmonary emboli on interobserver agreement in the inter- 80. Mastora I, Remy-Jardin M, Masson P, et al. Severity of acute pulmonary pretation of pulmonary angiography. AJR Am J Roentgenol embolism: evaluation of a new spiral CT angiographic score in corre- 1998;171(4):1085e9. lation with echocardiographic data. Eur Radiol 2003;13(1):29e35. 62. Castaner E, Gallardo X, Ballesteros E, et al. CT diagnosis of chronic pul- 81. Vedovati MC, Germini F, Agnelli G, et al. Prognostic role of embolic monary thromboembolism. RadioGraphics 2009;29(1):31e50 [discus- burden assessed at computed tomography angiography in patients with sion: 50e3]. acute pulmonary embolism: systematic review and meta-analysis. J 63. Ogo T. Balloon pulmonary angioplasty for inoperable chronic throm- Thromb Haemost 2013;11(12):2092e102. boembolic pulmonary hypertension. Curr Opin Pulm Med 82. Becattini C, Agnelli G, Vedovati MC, et al. Multidetector computed to- 2015;21(5):425e31. mography for acute pulmonary embolism: diagnosis and risk stratifi- 64. Schuemichen C. Pulmonary embolism: is multislice CT the method of cation in a single test. Eur Heart J 2011;32(13):1657e63. choice? Against. Eur J Nucl Med Mol Imaging 2005;32(1):107e12. 83. Furlan A, Aghayev A, Chang CC, et al. Short-term mortality in acute 65. Roach PJ, Schembri GP, Bailey DL. V/Q scanning using SPECT and SPECT/ pulmonary embolism: clot burden and signs of right heart dysfunction CT. J Nucl Med 2013;54(9):1588e96. at CT pulmonary angiography. Radiology 2012;265(1):283e93. 66. Schembri GP, Miller AE, Smart R. Radiation dosimetry and safety issues 84. Zhang LJ, Lu GM, Meinel FG, et al. Computed tomography of acute in the investigation of pulmonary embolism. Semin Nucl Med pulmonary embolism: state-of-the-art. Eur Radiol 2015;25(9):2547e57. 2010;40(6):442e54. 85. Kang DK, Thilo C, Schoepf UJ, et al. CT signs of right ventricular 67. Investigators P. Value of the ventilation/perfusion scan in acute pul- dysfunction: prognostic role in acute pulmonary embolism. JACC Car- monary embolism. Results of the prospective investigation of pulmo- diovasc Imaging 2011;4(8):841e9. nary embolism diagnosis (PIOPED). JAMA 1990;263(20):2753e9. 86. Truong QA, Massaro JM, Rogers IS, et al. Reference values for normal 68. Glaser JE, Chamarthy M, Haramati LB, et al. Successful and safe imple- pulmonary artery dimensions by noncontrast cardiac computed to- mentation of a trinary interpretation and reporting strategy for V/Q mography: the Framingham Heart Study. Circ Cardiovasc Imaging lung scintigraphy. J Nucl Med 2011;52(10):1508e12. 2012;5(1):147e54. 69. Bajc M, Neilly JB, Miniati M, et al. EANM guidelines for ventilation/ 87. Alhamad EH, Al-Boukai AA, Al-Kassimi FA, et al. Prediction of pulmonary perfusion scintigraphy: part 1. Pulmonary imaging with ventilation/ hypertension in patients with or without interstitial lung disease: reli- perfusion single photon emission tomography. Eur J Nucl Med Mol Im- ability of CT findings. Radiology 2011;260(3):875e83. aging 2009;36(8):1356e70. 88. Ng CS, Wells AU, Padley SP. A CT sign of chronic pulmonary arterial 70. Parker JA, Coleman RE, Grady E, et al. SNM practice guideline for lung hypertension: the ratio of main pulmonary artery to aortic diameter. J scintigraphy 4.0. J Nucl Med Technol 2012;40(1):57e65. Thorac Imaging 1999;14(4):270e8. 71. Sostman HD, Stein PD, Gottschalk A, et al. Acute pulmonary embolism: 89. Pena E, Dennie C, Veinot J, et al. Pulmonary hypertension: how the sensitivity and specificity of ventilationeperfusion scintigraphy in PIO- radiologist can help. RadioGraphics 2012;32(1):9e32. PED II study. Radiology 2008;246(3):941e6. 90. Tan RT, Kuzo R, Goodman LR, et al. Utility of CT scan evaluation for 72. Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pul- predicting pulmonary hypertension in patients with parenchymal lung monary angiography vs ventilationeperfusion lung scanning in patients disease. Medical College of Wisconsin Lung Transplant Group. Chest with suspected pulmonary embolism: a randomized controlled trial. 1998;113(5):1250e6. JAMA 2007;298(23):2743e53. 91. Stein PD, Woodard PK, Hull RD, et al. gadolinium-enhanced magnetic 73. Reinartz P, Wildberger JE, Schaefer W, et al. Tomographic imaging in the resonance angiography for detection of acute pulmonary embolism: an diagnosis of pulmonary embolism: a comparison between V/Q lung in-depth review. Chest 2003;124(6):2324e8. scintigraphy in SPECT technique and multislice spiral CT. J Nucl Med 92. Kruger S, Haage P, Hoffmann R, et al. Diagnosis of pulmonary arterial 2004;45(9):1501e8. hypertension and pulmonary embolism with magnetic resonance 74. Phillips JJ, Straiton J, Staff RT. Planar and SPECT ventilation/perfusion angiography. Chest 2001;120(5):1556e61. imaging and computed tomography for the diagnosis of pulmonary 93. Junqueira FP, Lima CM, Coutinho Jr AC, et al. Pulmonary arterial hyper- embolism: a systematic review and meta-analysis of the literature, and tension: an imaging review comparing MR pulmonary angiography and cost and dose comparison. Eur J Radiol 2015;84(7):1392e400. perfusion with multidetector CT angiography. Br J Radiol 75. Gutte H, Mortensen J, Jensen CV, et al. Detection of pulmonary embolism 2012;85(1019):1446e56. with combined ventilation-perfusion SPECT and low-dose CT: head-to- 94. Endrys J, Hayat N, Cherian G. Comparison of bronchopulmonary col- head comparison with multidetector CT angiography. J Nucl Med laterals and collateral blood flow in patients with chronic thrombo- 2009;50(12):1987e92. embolic and primary pulmonary hypertension. Heart 1997;78(2):171e6. 76. Tunariu N, Gibbs SJ, Win Z, et al. Ventilationeperfusion scintigraphy is 95. Glatz AC, Rome JJ, Small AJ, et al. Systemic-to-pulmonary collateral flow, more sensitive than multidetector CTPA in detecting chronic thrombo- as measured by cardiac magnetic resonance imaging, is associated with embolic pulmonary disease as a treatable cause of pulmonary hyper- acute post-Fontan clinical outcomes. Circ Cardiovasc Imaging tension. J Nucl Med 2007;48(5):680e4. 2012;5(2):218e25. 77. He J, Fang W, Lv B, et al. Diagnosis of chronic thromboembolic pulmo- 96. Beyar R, Dong SJ, Smith ER, et al. Ventricular interaction and septal nary hypertension: comparison of ventilation/perfusion scanning and deformation: a model compared with experimental data. Am J Physiol multidetector computed tomography pulmonary angiography with 1993;265(6 Pt 2):H2044e56. pulmonary angiography. Nucl Med Commun 2012;33(5):459e63. 97. Meysman M, Diltoer M, Raeve HD, et al. Chronic thromboembolic pul- 78. Seferian A, Helal B, Jais X, et al. Ventilation/perfusion lung scan in pul- monary hypertension and vascular transformation of the lymph node monary veno-occlusive disease. Eur Respir J 2012;40(1):75e83. sinuses. Eur Respir J 1997;10(5):1191e3.