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Advances in Pulmonary Embolism Imaging

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1 Advances in Pulmonary Embolism Imaging
Kelly MacLean; David Tso; Ferco Berger; Anja Reimann; Chris Davison; Joao Inacio; Ahmed Albuali; Savvas Nicolaou ASER 2010

2 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

3 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

4 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% ASER limits to 40 slides per presentation. Suggest tightening intro to make more succint Horlander KT; Mannino DM; Leeper KV. Arch Intern Med Jul; 163(14): Carson JL et al. N. Engl. J. Med May 7; 326(19):

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.

6 Pathophysiology Impaired gas exchange Hypotension
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 Discuss pathophysiology of tissue death, preload, RV strain Nakos G; Kitsiouli EI; Lekka ME. Am. J. Respir. Crit. Care Med Nov; 158(5 Pt 1): Goldhaber Z; Elliot CG. Circulation 2003; 108:

7 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): Stein PD et al. Am. J. Med Oct;120(10):871-9.

8 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 Incorporate this into a table with Signs & Symptoms together Goldhaber SZ; Visani L; De Rosa M. Lancet 1999 Apr 24;353(9162): Stein PD et al. Am. J. Med Oct;120(10):871-9.

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:

10 The Christopher Study - Outcomes
Perhaps cut out this table and stick with summaries points 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:

11 Modified Wells Criteria
Clinical symptoms of DVT (leg swelling, pain with palpation) 3.0 Other diagnosis less likely than PE Heart rate >100 1.5 Immobilization or surgery in previous 4 weeks Previous DVT/PE Hemoptysis 1.0 Malignancy PE Likely >4 PE Unlikely </= 4 Wells PS et al. Thromb Haemost 2000 Mar; 83(3):

12 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 Apr 20;140(8): De Monye W et al. Am. J. Respir. Crit. Care Med Feb 1;165(3):345-8. Perrier et al. Am. J. Respir. Crit. Care Med. 2003; 167:39-44.

13 The Christopher Study – Workup Algorithm
Zoom into MDCT Writing Group for the Christopher Study Investigators JAMA. 2006; 295:

14 Overview of Imaging Modalities for Pulmonary Embolism
Lower extremity venous ultrasonography Multidetector helical CT pulmonary angiography MRI Ventilation-perfusion scintigraphy (V/Q scan)

15 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 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%) Turkstra F; Kuijer PM; van Beek EJ; Brandjes DP; ten Cate JW; Buller HR. Ann Intern Med May 15;126(10):

16 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 Flow chart Anderson DR; Barnes D. Semin. Nucl. Med Nov;38(6)412-7.

17 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 David/Dr. Nicolaou – should I mention here anything about pros/cons of adding lower-limb CT venography? Stein PD et al. N. Engl. J. Med Jun 1;354(22):

18 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 Feb; 230:

19 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 Feb; 230:

20 MRI 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. 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 Incorporate PIOPED III Trial into limitations section next slide Kluge, A. et al. Am. J. Roentgenol. 2006;187:W7-W14 Stein PD et al. Ann Intern Med. 2010;152:

21 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 Mar 1;167(5): Epub 2002 Nov 21. Spuentrup E et al. Am. J. Respir. Crit. Care Med Aug 15;172(4): Epub 2005 Jun 3.

22 Ventilation-perfusion scintigraphy
PIOPED Study: Accuracy of V/Q scan versus reference standard (pulmonary angiogram) 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 95 86 56 66 28 15 40 4 Normal or near normal 6 2 The PIOPED Investigators. JAMA May 23-30;263(20):

23 V/Q Scan Advantages Limitations
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.

24 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%) CT- PA: spell out acronym CT able to determine other causes Anderson DR et al. JAMA Dec 19;298(23): Sostman DH et al. Radiology Jan 14;246:

25 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 Jan;242:15-21. Marik PE; Plante LA. N. Engl. J. Med. 2008;359:

26 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 Awaiting Charles Uh for protocols Need to get VGH protocols Schaefer-Prokop C; Prokop M. Eur. Radiol. Suppl. 2005;15(4):d37-d41.

27 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):

28 MDCT Findings C D B A Need to make arrows more accentuated, use “Shapes” under drawing tools in Powerpoint Make image bigger, 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)

29 Arrow indicating tram-track sign
Arrow indicating rim sign

30 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):

31 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): Goodman LR. Radiology. 2005;234(3) Glassroth J. JAMA. 2007;298(23):

32 Patient with pneumonectomy
Lingular subsegmental pulmonary embolism (arrow)

33 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 Increase afterload, can’t generate enough pressures Restate why contrast may end up in IVC Massive bilateral PE with signs of RV strain. Dilated RV with visible thrombus (arrow). Sanchez O et al. Eur. Heart J. 2008;29:1569–77.

34 Contrast seen in IVC, indicating RV strain
Mosaic attenuation – should use lung window Contrast seen in IVC, indicating RV strain Bilateral mosaic attenuation

35 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 Is it okay we use these slides – technically is this presentation for educational purposes? Question: How do we score clot burden?

36 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 Please have this in lung windows Massive PE with RV strain and mosaic attenuation (arrow) Wittram C et al. AJR 2006;186:S421-S429.

37

38 Diagnostic Imaging Algorithm
Where is CXR in this diagram. Also need to eliminate Venous U/S since it’s not done. Adapted from Agnelli G; Becattini C. N. Engl. J. Med. 2010;363:

39 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 Multiple thrombi in main PA with extensive clot burden. Perfusion defects seen on iodine mapping Pontana F et al. Acad. Radiol. 2008;15(12):1494.

40

41 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

42

43 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

44 References Agnelli GL Becattini C. Acute Pulmonary Embolism. N. Engl. J. Med. 2010;363: Anderson DR et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA Dec 19;298(23): Anderson DR; Barnes D. The use of leg venous ultrasonography for the diagnosis of pulmonary embolism. Semin. Nucl. Med 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): 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 Feb 1;165(3):345-8. Glassroth J. Imaging of Pulmonary Embolism – Too much of a Good Thing? JAMA. 2007;298(23): 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): Goldhaber Z; Elliot CG. Acute Pulmonary Embolism: Part I: Epidemiology, Pathophysiology, and Diagnosis. Circulation 2003;108; Goodman LR. Small pulmonary emboli: what do we know? Radiology. 2005;234(3) 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 Mar 1;167(5): Epub 2002 Nov 21. Horlander KT; Mannino DM; Leeper KV. Pulmonary embolism mortality in the United States, : an analysis using multiple-cause mortality data. Arch Intern Med Jul;163(14): 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): Macdonald S; Mayo J. Computed Tomography of Acute Pulmonary Embolism. Semin. Ultrasound CT. 2003;24(4): Marik PE; Plante LA. Venous thromboembolic disease and pregnancy. N. Engl. J. Med. 2008;359: 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 Nov;158(5 Pt 1): 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.

45 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 Feb;230: Sostman DH et al. Acute Pulmonary Embolism: Sensitivity and Specificity of Ventilation-Perfusion Scintigraphy in PIOPED II Study. Radiology Jan 14;246: 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 Aug 15;172(4): 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 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 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: 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 Jun 1;354(22): 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 Apr 20;140(8): 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: 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 May 23-30;263(20): 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 May 15;126(10): 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): 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:


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