Presentation on theme: "Advances in Pulmonary Embolism Imaging"— Presentation transcript:
1Advances in Pulmonary Embolism Imaging Kelly MacLean; David Tso; Ferco Berger;Anja Reimann; Chris Davison; Joao Inacio;Ahmed Albuali; Savvas NicolaouASER 2010
2ObjectivesIdentify the importance of a proper clinical scoring index exam in the ERReview of literature supporting CT for pulmonary embolism versus V/Q scanningAppropriate imaging of pulmonary embolism for pregnant patientsIllustrate MDCT technique, findings, artifacts, and clinical correlationsIntroduce new techniques and methods for assessing pulmonary embolism
3Outline Introduction Pathophysiology and clinical presentation Clinical prediction rules and D-dimer screeningDiagnostic imaging modalitiesImaging in pregnancyClinical implications of MDCT findingsDiagnostic imaging algorithmNew imaging approaches
4Introduction Acute PE is common High mortality rate if left untreated Clinical presentation is highly variable and non-specificDiagnosis requires appropriate and accurate imagingPrompt diagnosis and treatment can reduce mortality from 30% to 2-8%ASER limits to 40 slides per presentation. Suggest tightening intro to make more succintHorlander KT; Mannino DM; Leeper KV. Arch Intern Med Jul; 163(14):Carson JL et al. N. Engl. J. Med May 7; 326(19):
5PathophysiologyPE most commonly arise from thrombi in deep venous system of lower extremitiesIliofemoral vein thrombi most clinically recognized cause of PE50-80% of proximal vein thrombi originate distal to popliteal veinSize of PE determines location:Main pulmonary arteryLobar branchesSubsegmental emboliMoser, KM. Am. Rev. Respir. Dis. 1990; 141:235.Weinmann, EE; Salzman, EW. N. Engl. J. Med. 1994; 331:1630.
6Pathophysiology Impaired gas exchange Hypotension Ventilation/perfusion mismatchRelease of inflammatory mediators leads to surfactant dysfunction, atelectasis, alveolar hemorrhageIntrapulmonary shuntingHypotensionResults from increased PVR, RV dilatation, impaired LV filling, eventual impaired CODiscuss pathophysiology of tissue death, preload, RV strainNakos G; Kitsiouli EI; Lekka ME. Am. J. Respir. Crit. Care Med Nov; 158(5 Pt 1):Goldhaber Z; Elliot CG. Circulation 2003; 108:
7Clinical Presentation - Symptoms Dyspnea (73%) – usually acute onsetPleuritic 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.
8Clinical 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 PEIncorporate this into a table with Signs & Symptoms togetherGoldhaber SZ; Visani L; De Rosa M. Lancet 1999 Apr 24;353(9162):Stein PD et al. Am. J. Med Oct;120(10):871-9.
9Work-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 scanThe Christopher Study JAMA 2006Prospective cohort study of 3306 patients with clinically suspected PEWriting Group for the Christopher Study Investigators JAMA. 2006; 295:
10The Christopher Study - Outcomes Perhaps cut out this table and stick with summaries pointsLow risk of VTE when low clinical probability and normal D-dimer testingCT-PA effectively rules out PE without need for other imaging studiesFirst study to validate safety of dichotomized (modified) Wells Score vs. original Wells ScoreWriting Group for the Christopher Study Investigators JAMA. 2006; 295:
11Modified Wells Criteria Clinical symptoms of DVT (leg swelling, pain with palpation)3.0Other diagnosis less likely than PEHeart rate >1001.5Immobilization or surgery in previous 4 weeksPrevious DVT/PEHemoptysis1.0MalignancyPE Likely>4PE Unlikely</= 4Wells PS et al. Thromb Haemost 2000 Mar; 83(3):
12D-Dimer Screening Poor specificity and positive predictive value Sensitivity generally good but varies with:Type of assay usedLocation of PENormal D-dimer sufficient to exclude PE if low/moderate pretest probability (Wells Score)Cost-effectiveAvoids unnecessary imagingStein 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.
13The Christopher Study – Workup Algorithm Zoom into MDCTWriting Group for the Christopher Study Investigators JAMA. 2006; 295:
14Overview of Imaging Modalities for Pulmonary Embolism Lower extremity venous ultrasonographyMultidetector helical CT pulmonary angiographyMRIVentilation-perfusion scintigraphy (V/Q scan)
15Lower extremity venous ultrasonography Compression U/S = B-mode imaging onlyDuplex U/S = B-mode plus Doppler waveform analysisLimited vs.complete examIIliac, common femoral, femoral, popliteal, greater saphenous, calf veinsAdvantagesCostPortabilityMay avoid further diagnostic imaging if positiveLimitationsLow sensitivity and risk of false positivesNo consistent protocol for techniqueOperator dependantUsing positive U/S as diagnosis of PE would mean:Sensitivity 29%Specificity 97%Benefits: Avoid 14% of lung scans and 9% of angiogramsDrawbacks: 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):
16Venous Ultrasonography Recommendations of UseFirst-line if radiographic imaging contraindicated or not readily availableNot likely required in patient with negative CT-PAHelpful to rule out DVT in patient with non-diagnostic V/Q scanFlow chartAnderson DR; Barnes D. Semin. Nucl. Med Nov;38(6)412-7.
17Multidetector helical CT pulmonary angiography Increasingly the first-line imaging modalityPIOPED-II Study: 824 patients evaluated prospectively with multidetector CTA versus composite reference testSensitivity 83%Specificity 96%PPV = 96% with concordant clinical assessmentDavid/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):
18Multidetector helical CT pulmonary angiography – Advantages Diagnosis of alternative disease entitiesCoverage of entire chest with high spatial resolution in one breath holdHigh interobserver correlationAvailabilityImproved depiction of small peripheral emboliSchoepf J; Costello P. Radiology Feb; 230:
19Multidetector helical CT pulmonary angiography – Limitations Reader expertise requiredExpenseRequires precise timing of contrast bolusRadiation exposureNot portableContraindications to contrastRenal insufficiencyContrast allergySchoepf J; Costello P. Radiology Feb; 230:
20MRIImage: 59 y.o. male with severe dyspneaMR 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 TrialAccuracy of gadolinium-enhanced MR angiography in combination with venous phase venography in diagnosing acute PEInsufficient sensitivityHigh rate of technically inadequate imagesIncorporate PIOPED III Trial into limitations section next slideKluge, A. et al. Am. J. Roentgenol. 2006;187:W7-W14Stein PD et al. Ann Intern Med. 2010;152:
21MRI Advantages Lack of ionizing radiation Limitations Respiratory and cardiac motion artifactSuboptimal resolution for peripheral pulmonary arteriesComplicated blood flow patternsExperimental technology may have role in futureReal-time MR sequence without breath holdMolecular MRI with fibrin-specific contrast agentTapson, 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.
22Ventilation-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 studyScan ProbabilityClinical Probability of Pulmonary EmboliHighIntermediateLow958656662815404Normal or near normal62The PIOPED Investigators. JAMA May 23-30;263(20):
23V/Q Scan Advantages Limitations Excellent negative predictive value (97%)Can be used in patients with contraindication to contrast mediumLimitations30-50% of patients have non-diagnostic scan necessitating further investigationSostman HD et al. Radiology. 2008;246:941-6.
24CT-PA vs. V/Q scanDirectly compared in trial of 1417 patients with suspected PERandomized to CT-PA or V/Q scanMain outcome measure was development of symptomatic VTE post-negative testResult: CT-PA not inferior to V/Q scan for ruling out pulmonary embolismPIOPED IIhigher rate of non-diagnostic tests with V/Q Scan vs. CT-PA (26.5% vs. 6.2%)CT- PA: spell out acronymCT able to determine other causesAnderson DR et al. JAMA Dec 19;298(23):Sostman DH et al. Radiology Jan 14;246:
25Imaging in Pregnancy No validated clinical decision rules No consensus in evidence for diagnostic imaging algorithmBalance risk of radiation vs. risk of missed fatal diagnosis or unnecessary anticoagulationMDCT delivers higher radiation dose to mother but lower dose to fetus than V/Q scanningConsider low-dose CT-PA or reduced-dose lung scintigraphyStein P et al. Radiology Jan;242:15-21.Marik PE; Plante LA. N. Engl. J. Med. 2008;359:
26Multidetector-CT Technique Parameters vary by scanner equipmentContrast material bolusDuration of injection should approximate duration of scanDesired flow rate 3-5ml/sUsually 50-80mlBest results achieved if:Thin sectionsHigh and homogenous enhancement of pulmonary vesselsData acquisition in single breath holdAwaiting Charles Uh for protocolsNeed to get VGH protocolsSchaefer-Prokop C; Prokop M. Eur. Radiol. Suppl. 2005;15(4):d37-d41.
27Multidetector-CT Findings Partial or complete filling defects in lumen of pulmonary arteriesMost 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 planeRV strain indicated by straightening or leftward bowing of interventricular septumMacdonald S; Mayo J. Semin. Ultrasound CT. 2003;24(4):
28MDCT FindingsCDBANeed to make arrows more accentuated, use “Shapes” under drawing tools in PowerpointMake 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)
29Arrow indicating tram-track sign Arrow indicating rim sign
30Multidetector-CT: Artifacts Pseudo-filling defects or “pseudo-emboli” caused by:Suboptimal contrast enhancementMotion artifact – respiratory and cardiacVolume averaging of obliquely oriented vesselsNon-enhanced pulmonary veinsHilar lymph nodesAsymmetric pulmonary vascular resistanceMacdonald S; Mayo J. Semin. Ultrasound CT. 2003;24(4):
31Clinical relevance of MDCT findings I. Subsegmental Emboli Natural history largely unknownLack of evidence to guide managementSome suggest isolated subsegmental PE may not require treatment in appropriately selected subset of patientsCurrently treat on case-by-base basisLe Gal G et al. 2006;4(4):Goodman LR. Radiology. 2005;234(3)Glassroth J. JAMA. 2007;298(23):
32Patient with pneumonectomy Lingular subsegmental pulmonary embolism (arrow)
33Clinical Relevance of MDCT findings II. RV Strain Increased RV:LV ratio correlated with increased thrombus loadIncreased RV diastolic dimensions on axial CT correlate with worse outcome in acute PEIncrease afterload, can’t generate enough pressuresRestate why contrast may end up in IVCMassive bilateral PE with signs of RV strain. Dilated RV with visible thrombus (arrow).Sanchez O et al. Eur. Heart J. 2008;29:1569–77.
34Contrast seen in IVC, indicating RV strain Mosaic attenuation – should use lung windowContrast seen in IVC, indicating RV strainBilateral mosaic attenuation
35Clinical Relevance of MDCT findings III. Clot Burden Clot burden = pulmonary arterial obstruction indexConflicting evidence re: clinical relevanceProspective study of 105 patients with PE found no correlation between clot burden and all-cause mortality at 12 monthsPossible selection bias – patients with large clot burden may have died prior to CTPASingle-detector CTPA usedIs it okay we use these slides – technically is this presentation for educational purposes?Question: How do we score clot burden?
36Clinical Relevance of MDCT findings iv. Mosaic Perfusion Mosaic perfusion is an indirect sign of nonuniform pulmonary arterial perfusionNon-specific for acute PEDDx = chronic PE, emphysema, infection, compression/invasion of pulmonary artery, atelectasis, pleuritis, and pulmonary venous hypertensionNo evidence demonstrating clinical relevancePlease have this in lung windowsMassive PE with RV strain and mosaic attenuation (arrow)Wittram C et al. AJR 2006;186:S421-S429.
38Diagnostic 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:
39New Imaging Approaches Dual Energy Iodine Distribution MapsProvides functional and anatomic lung imagingDemonstrates perfusion defects beyond obstructive and non-obstructive clotsDiagnostic accuracy and inter/intra-observer variability requires further researchAdvantagesIndirect evaluation of peripheral pulmonary arterial bedDisadvantagesLonger data acquisition timeIncreased radiation exposureMultiple thrombi in main PA with extensive clot burden. Perfusion defects seen on iodine mappingPontana F et al. Acad. Radiol. 2008;15(12):1494.
41New Imaging Approaches Low dose MDCT using ultra high pitch techniqueUseful in patients who are unable to hold their breathTiming of contrast bolus even more criticalLeft lower lobe subsegmental embolism (arrow) with associated atelectasis using high-pitch technique
43ConclusionProper use of clinical prediction rules aids in better utilization of imaging studies and cost effectivenessMDCT-PA is preferred diagnostic techniqueV/Q scan for patients with contraindication to iodine contrastLow-dose CT-PA or reduced-dose lung scintigraphy in pregnancyDual energy CT can depict regional perfusion status as well as intravascular emboliHigh pitch low dose technique can reduce motion artifacts
44ReferencesAgnelli 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.
45References 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: