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076 advances in pulmonary imaging

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  • ASER limits to 40 slides per presentation. Suggest tightening intro to make more succint
  • Discuss pathophysiology of tissue death, preload, RV strain
  • Incorporate this into a table with Signs & Symptoms together
  • Perhaps cut out this table and stick with summaries points
  • Zoom into MDCT
  • Using positive U/S as diagnosis of PE would mean: Sensitivity 29% Specificity 97% Benefits: Avoid 14% of lung scans and 9% of angiograms Drawbacks: Unnecessary treatment in false positives (13%)
  • Flow chart
  • David/Dr. Nicolaou – should I mention here anything about pros/cons of adding lower-limb CT venography?
  • Incorporate PIOPED III Trial into limitations section next slide
  • CT- PA: spell out acronym CT able to determine other causes
  • Awaiting Charles Uh for protocols Need to get VGH protocols
  • Need to make arrows more accentuated, use “Shapes” under drawing tools in Powerpoint Make image bigger,
  • Increase afterload, can’t generate enough pressures Restate why contrast may end up in IVC
  • Mosaic attenuation – should use lung window
  • Is it okay we use these slides – technically is this presentation for educational purposes? Question: How do we score clot burden?
  • Please have this in lung windows
  • Where is CXR in this diagram. Also need to eliminate Venous U/S since it’s not done.

076 advances in pulmonary imaging 076 advances in pulmonary imaging Presentation Transcript

  • Advances in Pulmonary Embolism Imaging Kelly MacLean; David Tso; Ferco Berger; Anja Reimann; Chris Davison; Joao Inacio; Ahmed Albuali; Savvas Nicolaou ASER 2010
  • Objectives
    • Identify the importance of a proper clinical scoring index exam in the ER
    • Review of literature supporting CT for pulmonary embolism versus V/Q scanning
    • Appropriate imaging of pulmonary embolism for pregnant patients
    • Illustrate MDCT technique, findings, artifacts, and clinical correlations
    • Introduce new techniques and methods for assessing pulmonary embolism
  • Outline
    • Introduction
    • Pathophysiology and clinical presentation
    • Clinical prediction rules and D-dimer screening
    • Diagnostic imaging modalities
    • Imaging in pregnancy
    • Clinical implications of MDCT findings
    • Diagnostic imaging algorithm
    • New imaging approaches
  • Introduction
    • Acute PE is common
    • High mortality rate if left untreated
    • Clinical presentation is highly variable and non-specific
    • Diagnosis requires appropriate and accurate imaging
    • Prompt diagnosis and treatment can reduce mortality from 30% to 2-8%
    Horlander KT; Mannino DM; Leeper KV. Arch Intern Med. 2003 Jul; 163(14):1711-7. Carson JL et al. N. Engl. J. Med. 1992 May 7; 326(19):1240-5.
  • Pathophysiology
    • PE most commonly arise from thrombi in deep venous system of lower extremities
      • Iliofemoral vein thrombi most clinically recognized cause of PE
        • 50-80% of proximal vein thrombi originate distal to popliteal vein
    • Size of PE determines location:
        • Main pulmonary artery
        • Lobar branches
        • Subsegmental emboli
    Moser, KM. Am. Rev. Respir. Dis. 1990; 141:235. Weinmann, EE; Salzman, EW. N. Engl. J. Med. 1994; 331:1630.
  • Pathophysiology
    • Impaired gas exchange
      • Ventilation/perfusion mismatch
      • Release of inflammatory mediators leads to surfactant dysfunction, atelectasis, alveolar hemorrhage
      • Intrapulmonary shunting
    • Hypotension
      • Results from increased PVR, RV dilatation, impaired LV filling, eventual impaired CO
    Nakos G; Kitsiouli EI; Lekka ME. Am. J. Respir. Crit. Care Med. 1998 Nov; 158(5 Pt 1):1504-10. Goldhaber Z; Elliot CG. Circulation 2003; 108:2726-2729.
  • Clinical Presentation - Symptoms
    • Dyspnea (73%) – usually acute onset
    • Pleuritic chest pain (44%)
    • Calf pain/swelling (41-44%)
    • Orthopnea (28%)
    • Wheezing (21%)
    • Cough (20%)
    • Syncope (14%)
    • Hemoptysis (7%)
    Goldhaber SZ; Visani L; De Rosa M. Lancet 1999 Apr 24; 353(9162):1386-9. Stein PD et al. Am. J. Med. 2007 Oct;120(10):871-9.
  • Clinical Presentation – Signs
    • Tachypnea (53%)
    • Tachycardia (24%)
    • Rales (18%)
    • Decreased breath sounds (17%)
    • Accentuated P2 (15%)
    • JV distension (14%)
    • Signs and symptoms are highly variable, non- specific, and common in patients without PE
    Goldhaber SZ; Visani L; De Rosa M. Lancet 1999 Apr 24;353(9162):1386-9. Stein PD et al. Am. J. Med. 2007 Oct;120(10):871-9.
  • Work-up of patient with suspected PE
    • Stable patients should follow sequential diagnostic workup including:
      • Clinical probability assessment i.e. Wells Score
      • +/- D-dimer
      • +/- MDCT or V/Q scan
    • The Christopher Study JAMA 2006
    • Prospective cohort study of 3306 patients with clinically suspected PE
    Writing Group for the Christopher Study Investigators JAMA.  2006; 295:172-179.
  • The Christopher Study - Outcomes
    • Low risk of VTE when low clinical probability and normal D-dimer testing
    • CT-PA effectively rules out PE without need for other imaging studies
    • First study to validate safety of dichotomized (modified) Wells Score vs. original Wells Score
    Writing Group for the Christopher Study Investigators JAMA.  2006; 295:172-179.
  • Modified Wells Criteria Wells PS et al. Thromb Haemost 2000 Mar; 83(3):416-20. Clinical symptoms of DVT (leg swelling, pain with palpation) 3.0 Other diagnosis less likely than PE 3.0 Heart rate >100 1.5 Immobilization or surgery in previous 4 weeks 1.5 Previous DVT/PE 1.5 Hemoptysis 1.0 Malignancy 1.0 PE Likely >4 PE Unlikely </= 4
  • D-Dimer Screening
    • Poor specificity and positive predictive value
    • Sensitivity generally good but varies with:
      • Type of assay used
      • Location of PE
    • Normal D-dimer sufficient to exclude PE if low/moderate pretest probability (Wells Score)
    • Cost-effective
    • Avoids unnecessary imaging
    Stein PD et al. Ann Intern Med. 2004 Apr 20;140(8):589-602. De Monye W et al. Am. J. Respir. Crit. Care Med. 2002 Feb 1;165(3):345-8. Perrier et al. Am. J. Respir. Crit. Care Med. 2003; 167:39-44.
  • The Christopher Study – Workup Algorithm Writing Group for the Christopher Study Investigators JAMA.  2006; 295:172-179. Patient with clinically suspected pulmonary embolism Modified Wells Score PE Unlikely D-Dimer ELISA PE Likely MDCT-PA Indicated Normal Abnormal
  • Overview of Imaging Modalities for Pulmonary Embolism
    • Lower extremity venous ultrasonography
    • Multidetector helical CT pulmonary angiography
    • MRI
    • Ventilation-perfusion scintigraphy (V/Q scan)
  • Lower extremity venous ultrasonography
    • Compression U/S = B-mode imaging only
    • Duplex U/S = B-mode plus Doppler waveform analysis
    • Limited vs.complete exam
      • IIliac, common femoral, femoral, popliteal, greater saphenous, calf veins
      • Advantages
      • Cost
      • Portability
      • May avoid further diagnostic imaging if positive
      • Limitations
      • Low sensitivity and risk of false positives
      • No consistent protocol for technique
      • Operator dependant
    Turkstra F; Kuijer PM; van Beek EJ; Brandjes DP; ten Cate JW; Buller HR. Ann Intern Med. 1997 May 15;126(10):775-81.
  • Venous Ultrasonography
    • Recommendations of Use
    • First-line if radiographic imaging contraindicated or not readily available
    • Not likely required in patient with negative CT-PA
    • Helpful to rule out DVT in patient with non-diagnostic V/Q scan
    Anderson DR; Barnes D. Semin. Nucl. Med. 2008 Nov;38(6)412-7.
  • Multidetector helical CT pulmonary angiography
    • Increasingly the first-line imaging modality
    • PIOPED-II Study: 824 patients evaluated prospectively with multidetector CTA versus composite reference test
      • Sensitivity 83%
      • Specificity 96%
      • PPV = 96% with concordant clinical assessment
    Stein PD et al. N. Engl. J. Med. 2006 Jun 1;354(22):2317-27.
  • Multidetector helical CT pulmonary angiography – Advantages
    • Diagnosis of alternative disease entities
    • Coverage of entire chest with high spatial resolution in one breath hold
    • High interobserver correlation
    • Availability
    • Improved depiction of small peripheral emboli
    Schoepf J; Costello P. Radiology. 2004 Feb; 230:329-337.
  • Multidetector helical CT pulmonary angiography – Limitations
    • Reader expertise required
    • Expense
    • Requires precise timing of contrast bolus
    • Radiation exposure
    • Not portable
    • Contraindications to contrast
      • Renal insufficiency
      • Contrast allergy
    Schoepf J; Costello P. Radiology. 2004 Feb; 230:329-337.
  • MRI
    • PIOPED III Trial
      • Accuracy of gadolinium-enhanced MR angiography in combination with venous phase venography in diagnosing acute PE
      • Insufficient sensitivity
      • High rate of technically inadequate images
    Stein PD et al. Ann Intern Med. 2010;152:434-43. Image: 59 y.o. male with severe dyspnea MR angiogram depicts large amounts of embolic material ( arrowheads ) in right pulmonary artery, in right upper and lower lobes, and in left lingual pulmonary artery. Nonenhancing masses ( arrow ) are present in liver. Kluge, A. et al. Am. J. Roentgenol. 2006;187:W7-W14
  • MRI
    • Advantages
      • Lack of ionizing radiation
    • Limitations
      • Respiratory and cardiac motion artifact
      • Suboptimal resolution for peripheral pulmonary arteries
      • Complicated blood flow patterns
    • Experimental technology may have role in future
      • Real-time MR sequence without breath hold
      • Molecular MRI with fibrin-specific contrast agent
    Tapson, VF. N. Engl. J. Med. 1997; 336:1449. Haage P et al. Am. J. Respir. Crit. Care Med. 2003 Mar 1;167(5):729-34. Epub 2002 Nov 21. Spuentrup E et al. Am. J. Respir. Crit. Care Med. 2005 Aug 15;172(4):494-500. Epub 2005 Jun 3.
  • Ventilation-perfusion scintigraphy
    • PIOPED Study: Accuracy of V/Q scan versus reference standard (pulmonary angiogram)
    The PIOPED Investigators. JAMA. 1990 May 23-30;263(20):2753-9. Table: Likelihood of pulmonary embolism according to scan category and clinical probability in PIOPED study Scan Probability Clinical Probability of Pulmonary Emboli High Intermediate Low High 95 86 56 Intermediate 66 28 15 Low 40 15 4 Normal or near normal 0 6 2
  • V/Q Scan
    • Advantages
      • Excellent negative predictive value (97%)
      • Can be used in patients with contraindication to contrast medium
    • Limitations
      • 30-50% of patients have non-diagnostic scan necessitating further investigation
    Sostman HD et al. Radiology. 2008;246:941-6.
  • CT-PA vs. V/Q scan
    • Directly compared in trial of 1417 patients with suspected PE
    • Randomized to CT-PA or V/Q scan
    • Main outcome measure was development of symptomatic VTE post-negative test
    • Result: CT-PA not inferior to V/Q scan for ruling out pulmonary embolism
    • PIOPED II
      • higher rate of non-diagnostic tests with V/Q Scan vs. CT-PA (26.5% vs. 6.2%)
    Anderson DR et al. JAMA. 2007 Dec 19;298(23):2743-53. Sostman DH et al. Radiology. 2008 Jan 14;246:941-946.
  • Imaging in Pregnancy
    • No validated clinical decision rules
    • No consensus in evidence for diagnostic imaging algorithm
    • Balance risk of radiation vs. risk of missed fatal diagnosis or unnecessary anticoagulation
    • MDCT delivers higher radiation dose to mother but lower dose to fetus than V/Q scanning
    • Consider low-dose CT-PA or reduced-dose lung scintigraphy
    Stein P et al. Radiology. 2007 Jan;242:15-21. Marik PE; Plante LA. N. Engl. J. Med. 2008;359:2025-33.
  • Multidetector-CT Technique
    • Parameters vary by scanner equipment
    • Contrast material bolus
      • Duration of injection should approximate duration of scan
      • Desired flow rate 3-5ml/s
      • Usually 50-80ml
    • Best results achieved if:
      • Thin sections
      • High and homogenous enhancement of pulmonary vessels
      • Data acquisition in single breath hold
    Schaefer-Prokop C; Prokop M. Eur. Radiol. Suppl. 2005;15(4):d37-d41.
  • Multidetector-CT Findings
    • Partial or complete filling defects in lumen of pulmonary arteries
      • Most reliable sign is filling defect forming acute angle with vessel wall with defect outlined by contrast material
      • “ Tram-track sign”
        • Parallel lines of contrast surrounding thrombus in vessel that travels in transverse plane
      • “ Rim sign”
        • Contrast surrounding thrombus in vessel that travels orthogonal to transverse plane
    • RV strain indicated by straightening or leftward bowing of interventricular septum
    Macdonald S; Mayo J. Semin. Ultrasound CT. 2003;24(4):271-231.
  • MDCT Findings Large saddle thrombus with extensive clot burden. Arrows demonstrating tram-track sign (A), rim sign (B), complete filling defect (C), and a fully non-contrasted vessel (D) A B C D
  • Arrow indicating rim sign Arrow indicating tram-track sign
  • Multidetector-CT: Artifacts
    • Pseudo-filling defects or “pseudo-emboli” caused by:
      • Suboptimal contrast enhancement
      • Motion artifact – respiratory and cardiac
      • Volume averaging of obliquely oriented vessels
      • Non-enhanced pulmonary veins
      • Hilar lymph nodes
      • Asymmetric pulmonary vascular resistance
    Macdonald S; Mayo J. Semin. Ultrasound CT. 2003;24(4):231-271.
  • Clinical relevance of MDCT findings I. Subsegmental Emboli
    • Natural history largely unknown
    • Lack of evidence to guide management
    • Some suggest isolated subsegmental PE may not require treatment in appropriately selected subset of patients
    • Currently treat on case-by-base basis
    Le Gal G et al. 2006;4(4):724-731. Goodman LR. Radiology. 2005;234(3)654-658. Glassroth J. JAMA. 2007;298(23):2788-2789.
  • Patient with pneumonectomy Lingular subsegmental pulmonary embolism (arrow)
  • Clinical Relevance of MDCT findings II. RV Strain
    • Increased RV:LV ratio correlated with increased thrombus load
    • Increased RV diastolic dimensions on axial CT correlate with worse outcome in acute PE
    Sanchez O et al. Eur. Heart J. 2008;29:1569–77. Massive bilateral PE with signs of RV strain. Dilated RV with visible thrombus (arrow).
  • Contrast seen in IVC, indicating RV strain Bilateral mosaic attenuation
  • Clinical Relevance of MDCT findings III. Clot Burden
    • Clot burden = pulmonary arterial obstruction index
    • Conflicting evidence re: clinical relevance
    • Prospective study of 105 patients with PE found no correlation between clot burden and all-cause mortality at 12 months
      • Possible selection bias – patients with large clot burden may have died prior to CTPA
      • Single-detector CTPA used
  • Clinical Relevance of MDCT findings iv. Mosaic Perfusion
    • Mosaic perfusion is an indirect sign of nonuniform pulmonary arterial perfusion
      • Non-specific for acute PE
      • DDx = chronic PE, emphysema, infection, compression/invasion of pulmonary artery, atelectasis, pleuritis, and pulmonary venous hypertension
      • No evidence demonstrating clinical relevance
    Wittram C et al. AJR 2006;186:S421-S429. Massive PE with RV strain and mosaic attenuation (arrow)
  •  
  • Diagnostic Imaging Algorithm Adapted from Agnelli G; Becattini C. N. Engl. J. Med. 2010;363:266-74. Elevated D-Dimer or High clinical probability MDCT-PA V/Q Scan if contraindication to contrast Negative PE confirmed May consider venous U/S but will be positive in less than 1% of patients Diagnostic Non-diagnostic PE confirmed PE ruled out Venous U/S
  • New Imaging Approaches
    • Dual Energy Iodine Distribution Maps
      • Provides functional and anatomic lung imaging
      • Demonstrates perfusion defects beyond obstructive and non-obstructive clots
      • Diagnostic accuracy and inter/intra-observer variability requires further research
      • Advantages
        • Indirect evaluation of peripheral pulmonary arterial bed
      • Disadvantages
        • Longer data acquisition time
        • Increased radiation exposure
    Pontana F et al. Acad. Radiol. 2008;15(12):1494. Multiple thrombi in main PA with extensive clot burden. Perfusion defects seen on iodine mapping
  •  
  • New Imaging Approaches
    • Low dose MDCT using ultra high pitch technique
    • Useful in patients who are unable to hold their breath
    • Timing of contrast bolus even more critical
    Left lower lobe subsegmental embolism (arrow) with associated atelectasis using high-pitch technique
  •  
  • Conclusion
    • Proper use of clinical prediction rules aids in better utilization of imaging studies and cost effectiveness
    • MDCT-PA is preferred diagnostic technique
    • V/Q scan for patients with contraindication to iodine contrast
    • Low-dose CT-PA or reduced-dose lung scintigraphy in pregnancy
    • Dual energy CT can depict regional perfusion status as well as intravascular emboli
    • High pitch low dose technique can reduce motion artifacts
  • References
    • Agnelli GL Becattini C. Acute Pulmonary Embolism. N. Engl. J. Med. 2010;363:266-74.
    • Anderson DR et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007 Dec 19;298(23):2743-53.
    • Anderson DR; Barnes D. The use of leg venous ultrasonography for the diagnosis of pulmonary embolism. Semin. Nucl. Med. 2008 Nov;38(6)412-7.
    • Carson JL; Kelly MA; Duff A, et al. The clinical course of pulmonary embolism. N Engl J Med 1992 May 7;326(19):1240-5.
    • Chatellier G et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur. Heart J. 2008;29:1569–77.
    • De Monye W; Sanson BJ; Mac Gillavry MR; Pattynama PM; Buller HR; van den Berg-Huysmans AA; Huisman MV. Embolus location affects the sensitivity of a rapid quantitative D-dimer assay in the diagnosis of pulmonary embolism Am. J. Respir. Crit. Care Med. 2002 Feb 1;165(3):345-8.
    • Glassroth J. Imaging of Pulmonary Embolism – Too much of a Good Thing? JAMA. 2007;298(23):2788-2789.
    • Goldhaber SZ; Visani L; De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999 Apr 24;353(9162):1386-9.
    • Goldhaber Z; Elliot CG. Acute Pulmonary Embolism: Part I: Epidemiology, Pathophysiology, and Diagnosis. Circulation 2003;108;2726-2729.
    • Goodman LR. Small pulmonary emboli: what do we know? Radiology. 2005;234(3)654-658.
    • Haage P; Piroth W; Krombach G; Karaagac S; Schaffter T; Gunther RW; Bucker A. Pulmonary embolism: comparison of angiography with spiral computed tomography, magnetic resonance angiography, and real-time magnetic resonance imaging. Am. J. Respir. Crit. Care Med. 2003 Mar 1;167(5):729-34. Epub 2002 Nov 21.
    • Horlander KT; Mannino DM; Leeper KV. Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. Arch Intern Med. 2003 Jul;163(14):1711-7.
    • Kluge, A. et al. Acute Pulmonary Embolism to the Subsegmental Level: Diagnostic Accuracy of Three MRI Techniques Compared with 16-MDCT. Am. J. Roentgenol. 2006;187:W7-W14.
    • Le Gal G; Righini M; Parent F: Van Strijens M; Couturaud F. Diagnosis and management of subsegmental pulmonary embolism. J. Thromb Haemost 2006;4(4):724-731.
    • Macdonald S; Mayo J. Computed Tomography of Acute Pulmonary Embolism. Semin. Ultrasound CT. 2003;24(4):271-231.
    • Marik PE; Plante LA. Venous thromboembolic disease and pregnancy. N. Engl. J. Med. 2008;359:2025-33.
    • Moser KM. Venous thromboembolism. Am. Rev. Respir. Dis. 1990;141:235.
    • Nakos G; Kitsiouli EI; Lekka ME. Bronchoalveolar lavage alterations in pulmonary embolism. Am. J. Respir. Crit. Care Med. 1998 Nov;158(5 Pt 1):1504-10.
    • Perrier et al. Cost-Effectiveness Analysis of Diagnostic Strategies for Suspected Pulmonary Embolism Including Helical Computed Tomography. Am. J. Respir. Crit. Care Med. 2003;167:39-44.
    • Pontana F; Faivre BP; Remy-Jardin M et al. Lung Perfusion with Dual-energy Multidetector-row CT (MDCT): Feasibility for the Evaluation of Acute Pulmonary Embolism in 117 Consecutive Patients. Acad. Radiol. 2008;15(12):1494.
  • References
    • Sanchez O; Trinquart L; Colombet I; Duriex P; Huisman MV.
    • Schaefer-Prokop C; Prokop M. MDCT for the diagnosis of acute pulmonary embolism. Eur. Radiol. Suppl. 2005;15(4):d37-d41.
    • Schoepf J; Costello P. CT Angiography for Diagnosis of Pulmonary Embolism: State of the Art. Radiology. 2004 Feb;230:329-337.
    • Sostman DH et al. Acute Pulmonary Embolism: Sensitivity and Specificity of Ventilation-Perfusion Scintigraphy in PIOPED II Study. Radiology. 2008 Jan 14;246:941-946.
    • Sostman HD; Stein PD; Gottschalk A; Matta F; Hull R; Goodman L. Acute pulmonary embolism: sensitivity and specificity of ventilation-perfusion scintigraphy in PIOPED II study. Radiology. 2008;246:941-6.
    • Spuentrup E; Katoh M; Wiethoff AJ; Parsons EC Jr; Botnar RM; Mahnken AH; Gunther RW; Buecker A. Molecular Magnetic Resonance Imaging of Pulmonary Emboli with a Fibrin-specific Contrast Agent. Am. J. Respir. Crit. Care Med. 2005 Aug 15;172(4):494-500. Epub 2005 Jun 3.
    • Stein P; Woodard P; Weg J, et al. Diagnostic Pathways in Acute Pulmonary Embolism: Recommendations of The PIOPED II Investigators. Radiology. 2007 Jan;242:15-21.
    • Stein PD; Beemath A; Matta F; Weg JG; Yusen RD; Hales CA; Hull RD; Leeper KV Jr; Sostman HD; Tapson VF; Buckley JD; Gottschalk A; Goodman LR; Wakefied TW; Woodard PK. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am. J. Med. 2007 Oct;120(10):871-9.
    • Stein PD; Chenevert TL; Folwer Se et al. Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III). Ann Intern Med. 2010;152:434-43.
    • Stein PD; Fowler SE; Goodman LR; Gottschalk A; Hales CA; Hull RD; Leeper KV Jr; Popovich J Jr; Quinn DA; Sos TA; Sostman HD; Tapson VF; Wakefield TW; Weg JG; Woodard PK. Multidetector computed tomography for acute pulmonary embolism. N. Engl. J. Med. 2006 Jun 1;354(22):2317-27.
    • Stein PD; Hull RD; Patel KC; Olson RE; Ghali WA; Brant R; Biel RK; Bharadia V; Kalra NK. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med. 2004 Apr 20;140(8):589-602.
    • Subramaniam, RM et al. Pulmonary Embolism Outcome: A Prospective Evaluation of CT Pulmonary Angiographic Clot Burden Score and ECG Score. Am. J. Roentgenol. 2008;190:1599-1604.
    • Tapson VF. Pulmonary embolism — new diagnostic approaches. N. Engl. J. Med. 1997;336:1449.
    • The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990 May 23-30;263(20):2753-9.
    • Turkstra F; Kuijer PM; van Beek EJ; Brandjes DP; ten Cate JW; Buller HR. Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism. Ann Intern Med. 1997 May 15;126(10):775-81.
    • Weinmann EE; Salzman EW. Deep-vein thrombosis. N. Engl. J. Med. 1994;331:1630.
    • Wells PS; Anderson DR; Rodger M et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000 Mar;83(3):416-20.
    • Wittram C et al. Acute and Chronic Pulmonary Emboli: Angiography–CT Correlation. AJR 2006;186:S421-S429.
    • Writing Group for the Christopher Study Investigators. Effectiveness of Managing Suspected Pulmonary Embolism Using an Algorithm Combining Clinical Probability, D-Dimer Testing, and Computed Tomography. JAMA.  2006;295:172-179.