076 advances in pulmonary imaging
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Advances in Pulmonary Advances in Pulmonary Embolism ImagingEmbolism Imaging
Kelly MacLean; David Tso; Ferco Berger; Kelly MacLean; David Tso; Ferco Berger; Anja Reimann; Chris Davison; Joao Inacio; Anja Reimann; Chris Davison; Joao Inacio;
Ahmed Albuali; Savvas NicolaouAhmed Albuali; Savvas Nicolaou ASER 2010ASER 2010
ObjectivesObjectives Identify the importance of a proper clinical scoring Identify the importance of a proper clinical scoring
index exam in the ERindex exam in the ER Review of literature supporting CT for pulmonary Review of literature supporting CT for pulmonary
embolism versus V/Q scanningembolism versus V/Q scanning Appropriate imaging of pulmonary embolism for Appropriate imaging of pulmonary embolism for
pregnant patientspregnant patients Illustrate MDCT technique, findings, artifacts, and Illustrate MDCT technique, findings, artifacts, and
clinical correlationsclinical correlations Introduce new techniques and methods for Introduce new techniques and methods for
assessing pulmonary embolismassessing pulmonary embolism
OutlineOutline IntroductionIntroduction Pathophysiology and clinical presentationPathophysiology and clinical presentation Clinical prediction rules and D-dimer screeningClinical prediction rules and D-dimer screening Diagnostic imaging modalities Diagnostic imaging modalities Imaging in pregnancyImaging in pregnancy Clinical implications of MDCT findingsClinical implications of MDCT findings Diagnostic imaging algorithmDiagnostic imaging algorithm New imaging approachesNew imaging approaches
IntroductionIntroduction
Acute PE is common Acute PE is common High mortality rate if left untreatedHigh mortality rate if left untreated Clinical presentation is highly variable and non-Clinical presentation is highly variable and non-
specificspecific Diagnosis requires appropriate and accurate Diagnosis requires appropriate and accurate
imagingimaging Prompt diagnosis and treatment can reduce Prompt diagnosis and treatment can reduce
mortality from 30% to 2-8%mortality from 30% to 2-8%
Horlander KT; Mannino DM; Leeper KV. Arch Intern Med. 2003 Jul; Horlander KT; Mannino DM; Leeper KV. Arch Intern Med. 2003 Jul; 163(14):1711-7.163(14):1711-7.
Carson JL et al. N. Engl. J. Med. 1992 May 7; 326(19):1240-5.Carson JL et al. N. Engl. J. Med. 1992 May 7; 326(19):1240-5.
Pathophysiology Pathophysiology
PE most commonly arise from thrombi in PE most commonly arise from thrombi in deep venous system of lower extremitiesdeep venous system of lower extremities Iliofemoral vein thrombi most clinically Iliofemoral vein thrombi most clinically
recognized cause of PErecognized cause of PE50-80% of proximal vein thrombi originate distal to 50-80% of proximal vein thrombi originate distal to
popliteal veinpopliteal vein
Size of PE determines location:Size of PE determines location:Main pulmonary arteryMain pulmonary arteryLobar branchesLobar branchesSubsegmental emboliSubsegmental emboli
Moser, KM. Am. Rev. Respir. Dis. 1990; 141:235.Moser, KM. Am. Rev. Respir. Dis. 1990; 141:235.Weinmann, EE; Salzman, EW. N. Engl. J. Med. 1994; Weinmann, EE; Salzman, EW. N. Engl. J. Med. 1994;
331:1630.331:1630.
PathophysiologyPathophysiology Impaired gas exchange Impaired gas exchange
Ventilation/perfusion mismatchVentilation/perfusion mismatchRelease of inflammatory mediators leads to Release of inflammatory mediators leads to
surfactant dysfunction, atelectasis, alveolar surfactant dysfunction, atelectasis, alveolar hemorrhagehemorrhage
Intrapulmonary shuntingIntrapulmonary shuntingHypotensionHypotension
Results from increased PVR, RV dilatation, Results from increased PVR, RV dilatation, impaired LV filling, eventual impaired COimpaired 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 - Clinical Presentation - SymptomsSymptoms
Dyspnea (73%) – usually acute onsetDyspnea (73%) – usually acute onsetPleuritic chest pain (44%)Pleuritic chest pain (44%)Calf pain/swelling (41-44%)Calf pain/swelling (41-44%)Orthopnea (28%)Orthopnea (28%)Wheezing (21%)Wheezing (21%)Cough (20%)Cough (20%)Syncope (14%)Syncope (14%)Hemoptysis (7%)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 – SignsClinical Presentation – Signs
Tachypnea (53%)Tachypnea (53%) Tachycardia (24%)Tachycardia (24%) Rales (18%)Rales (18%) Decreased breath sounds (17%)Decreased breath sounds (17%) Accentuated P2 (15%)Accentuated P2 (15%) JV distension (14%)JV distension (14%)
Signs and symptoms are highly variable, non- Signs and symptoms are highly variable, non- specific, and common in patients without PEspecific, 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 Work-up of patient with suspected PEsuspected PE
Stable patients should follow sequential Stable patients should follow sequential diagnostic workup including:diagnostic workup including:Clinical probability assessment i.e. Wells Clinical probability assessment i.e. Wells
ScoreScore+/- D-dimer+/- D-dimer+/- MDCT or V/Q scan +/- MDCT or V/Q scan
The Christopher Study JAMA 2006The Christopher Study JAMA 2006Prospective cohort study of 3306 patients Prospective cohort study of 3306 patients
with clinically suspected PEwith clinically suspected PE
Writing Group for the Christopher Study Investigators JAMA. 2006; 295:172-179.
The Christopher Study - OutcomesThe 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 CriteriaModified Wells Criteria
Clinical symptoms of DVT (leg swelling, pain with Clinical symptoms of DVT (leg swelling, pain with palpation)palpation)
3.03.0
Other diagnosis less likely than PEOther diagnosis less likely than PE 3.03.0
Heart rate >100Heart rate >100 1.51.5
Immobilization or surgery in previous 4 weeksImmobilization or surgery in previous 4 weeks 1.51.5
Previous DVT/PEPrevious DVT/PE 1.51.5
HemoptysisHemoptysis 1.01.0
MalignancyMalignancy 1.01.0
PE LikelyPE Likely >4>4
PE UnlikelyPE Unlikely </= 4</= 4
Wells PS et al. Thromb Haemost 2000 Mar; 83(3):416-20.
D-Dimer ScreeningD-Dimer Screening Poor specificity and positive predictive valuePoor specificity and positive predictive value Sensitivity generally good but varies with:Sensitivity generally good but varies with:
Type of assay usedType of assay used Location of PE Location of PE
Normal D-dimer sufficient to exclude PE if Normal D-dimer sufficient to exclude PE if low/moderate pretest probability (Wells Score)low/moderate pretest probability (Wells Score)
Cost-effectiveCost-effective Avoids unnecessary imagingAvoids unnecessary imaging
Stein PD et al. Ann Intern Med. 2004 Apr 20;140(8):589-602.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 The Christopher Study – Workup AlgorithmAlgorithm
Patient with clinically suspected pulmonary embolism
Modified Wells Score
PE Unlikely
D-Dimer ELISA
PE Likely
MDCT-PA Indicated
Normal Abnormal
Writing Group for the Christopher Study Investigators JAMA. 2006; 295:172-179.
Lower extremity venous ultrasonographyLower extremity venous ultrasonography Compression U/S = B-mode imaging onlyCompression U/S = B-mode imaging only Duplex U/S = B-mode plus Doppler waveform analysisDuplex U/S = B-mode plus Doppler waveform analysis Limited vs.complete examLimited vs.complete exam
IIliac, common femoral, femoral, popliteal, greater saphenous, IIliac, common femoral, femoral, popliteal, greater saphenous, calf veinscalf veins
AdvantagesAdvantages CostCost PortabilityPortability May avoid further diagnostic imaging if positiveMay avoid further diagnostic imaging if positiveLimitationsLimitations Low sensitivity and risk of false positivesLow sensitivity and risk of false positives No consistent protocol for techniqueNo consistent protocol for technique Operator dependantOperator 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 UltrasonographyVenous 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 Multidetector helical CT pulmonary angiographyangiography
Increasingly the first-line imaging modalityIncreasingly the first-line imaging modalityPIOPED-II Study: 824 patients evaluated PIOPED-II Study: 824 patients evaluated
prospectively with multidetector CTA prospectively with multidetector CTA versus composite reference testversus composite reference testSensitivity 83%Sensitivity 83%Specificity 96%Specificity 96%PPV = 96% with concordant clinical PPV = 96% with concordant clinical
assessment assessment
Stein PD et al. N. Engl. J. Med. 2006 Jun 1;354(22):2317-27.
Multidetector helical CT pulmonary Multidetector helical CT pulmonary angiography – angiography – AdvantagesAdvantages
Diagnosis of alternative disease entitiesDiagnosis of alternative disease entitiesCoverage of entire chest with high spatial Coverage of entire chest with high spatial
resolution in one breath holdresolution in one breath holdHigh interobserver correlationHigh interobserver correlationAvailabilityAvailability Improved depiction of small peripheral Improved depiction of small peripheral
emboliemboli
Schoepf J; Costello P. Radiology. 2004 Feb; 230:329-337.
Multidetector helical CT pulmonary Multidetector helical CT pulmonary angiography – angiography – LimitationsLimitations
Reader expertise requiredReader expertise requiredExpenseExpenseRequires precise timing of contrast bolusRequires precise timing of contrast bolusRadiation exposureRadiation exposureNot portableNot portableContraindications to contrastContraindications to contrast
Renal insufficiencyRenal insufficiencyContrast allergyContrast allergy
Schoepf J; Costello P. Radiology. 2004 Feb; 230:329-337.
MRIMRI PIOPED III Trial PIOPED III Trial
Accuracy of gadolinium-Accuracy of gadolinium-enhanced MR enhanced MR angiography in angiography in combination with combination with venous phase venous phase venography in venography in diagnosing acute PEdiagnosing acute PE
Insufficient sensitivity Insufficient sensitivity High rate of technically High rate of technically
inadequate imagesinadequate 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
MRIMRIAdvantagesAdvantages
Lack of ionizing radiationLack of ionizing radiation
LimitationsLimitations Respiratory and cardiac motion artifactRespiratory and cardiac motion artifact Suboptimal resolution for peripheral pulmonary arteriesSuboptimal resolution for peripheral pulmonary arteries Complicated blood flow patternsComplicated blood flow patterns
Experimental technology may have role in future Experimental technology may have role in future Real-time MR sequence without breath holdReal-time MR sequence without breath hold Molecular MRI with fibrin-specific contrast agentMolecular 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.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 scintigraphyVentilation-perfusion scintigraphy
PIOPED Study: Accuracy of V/Q scan versus PIOPED Study: Accuracy of V/Q scan versus reference standard (pulmonary angiogram)reference standard (pulmonary angiogram)
Scan ProbabilityScan ProbabilityClinical Probability of Pulmonary EmboliClinical Probability of Pulmonary Emboli
HighHigh IntermediateIntermediate LowLow
HighHigh 9595 8686 5656IntermediateIntermediate 6666 2828 1515LowLow 4040 1515 44Normal or near Normal or near normal normal
00 66 22
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
V/Q ScanV/Q Scan
AdvantagesAdvantagesExcellent negative predictive value (97%)Excellent negative predictive value (97%)Can be used in patients with contraindication Can be used in patients with contraindication
to contrast mediumto contrast mediumLimitationsLimitations
30-50% of patients have non-diagnostic scan 30-50% of patients have non-diagnostic scan necessitating further investigationnecessitating further investigation
Sostman HD et al. Radiology. 2008;246:941-6.
CT-PA vs. V/Q scanCT-PA vs. V/Q scan
Directly compared in trial of 1417 patients with Directly compared in trial of 1417 patients with suspected PEsuspected PE
Randomized to CT-PA or V/Q scanRandomized to CT-PA or V/Q scan Main outcome measure was development of Main outcome measure was development of
symptomatic VTE post-negative testsymptomatic VTE post-negative test Result: CT-PA not inferior to V/Q scan for ruling Result: CT-PA not inferior to V/Q scan for ruling
out pulmonary embolismout pulmonary embolism
PIOPED IIPIOPED II higher rate of non-diagnostic tests with V/Q Scan vs. higher rate of non-diagnostic tests with V/Q Scan vs.
CT-PA (26.5% vs. 6.2%)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 PregnancyImaging in Pregnancy No validated clinical decision rulesNo validated clinical decision rules No consensus in evidence for diagnostic No consensus in evidence for diagnostic
imaging algorithmimaging algorithm Balance risk of radiation vs. risk of missed fatal Balance risk of radiation vs. risk of missed fatal
diagnosis or unnecessary anticoagulationdiagnosis or unnecessary anticoagulation MDCT delivers higher radiation dose to mother MDCT delivers higher radiation dose to mother
but lower dose to fetus than V/Q scanningbut lower dose to fetus than V/Q scanning Consider low-dose CT-PA or reduced-dose lung Consider low-dose CT-PA or reduced-dose lung
scintigraphyscintigraphy
Stein P et al. Radiology. 2007 Jan;242:15-21.Stein P et al. Radiology. 2007 Jan;242:15-21.
Marik PE; Plante LA. N. Engl. J. Med. 2008;359:2025-33.Marik PE; Plante LA. N. Engl. J. Med. 2008;359:2025-33.
Multidetector-CTMultidetector-CTTechniqueTechnique
Parameters vary by scanner equipmentParameters vary by scanner equipment Contrast material bolusContrast material bolus
Duration of injection should approximate duration of Duration of injection should approximate duration of scanscan
Desired flow rate 3-5ml/sDesired flow rate 3-5ml/s Usually 50-80mlUsually 50-80ml
Best results achieved if:Best results achieved if: Thin sectionsThin sections High and homogenous enhancement of pulmonary High and homogenous enhancement of pulmonary
vesselsvessels Data acquisition in single breath holdData acquisition in single breath hold
Schaefer-Prokop C; Prokop M. Eur. Radiol. Suppl. 2005;15(4):d37-d41.
Multidetector-CTMultidetector-CTFindingsFindings
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.
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
CD
MDCT FindingsMDCT Findings
Arrow indicating rim sign Arrow indicating tram-track sign
Multidetector-CT: ArtifactsMultidetector-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 resistance
Macdonald S; Mayo J. Semin. Ultrasound CT. 2003;24(4):231-271.
Clinical relevance of MDCT findingsClinical relevance of MDCT findingsI. Subsegmental EmboliI. Subsegmental Emboli
Natural history largely unknownNatural history largely unknown Lack of evidence to guide managementLack of evidence to guide management Some suggest isolated subsegmental PE may Some suggest isolated subsegmental PE may
not require treatment in appropriately selected not require treatment in appropriately selected subset of patientssubset of patients
Currently treat on case-by-base basisCurrently 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 findingsClinical Relevance of MDCT findings II. RV StrainII. 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 Clinical Relevance of MDCT findings III. Clot BurdenIII. Clot Burden
Clot burden = pulmonary arterial obstruction indexClot burden = pulmonary arterial obstruction index Conflicting evidence re: clinical relevanceConflicting evidence re: clinical relevance Prospective study of 105 patients with PE found no Prospective study of 105 patients with PE found no
correlation between clot burden and all-cause correlation between clot burden and all-cause mortality at 12 monthsmortality at 12 monthsPossible selection bias – patients with large clot Possible selection bias – patients with large clot
burden may have died prior to CTPAburden may have died prior to CTPASingle-detector CTPA usedSingle-detector CTPA used
Clinical Relevance of MDCT findingsClinical Relevance of MDCT findingsiv. Mosaic Perfusioniv. 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 AlgorithmDiagnostic Imaging Algorithm
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
Adapted from Agnelli G; Becattini C. N. Engl. J. Med. 2010;363:266-74.
New Imaging ApproachesNew Imaging Approaches Dual Energy Iodine Distribution MapsDual Energy Iodine Distribution Maps
Provides functional and anatomic Provides functional and anatomic lung imaginglung imaging
Demonstrates perfusion defects Demonstrates perfusion defects beyond obstructive and non-beyond obstructive and non-obstructive clotsobstructive clots
Diagnostic accuracy and Diagnostic accuracy and inter/intra-observer variability inter/intra-observer variability requires further researchrequires further research
AdvantagesAdvantages Indirect evaluation of Indirect evaluation of
peripheral pulmonary arterial peripheral pulmonary arterial bedbed
DisadvantagesDisadvantages Longer data acquisition time Longer data acquisition time Increased radiation exposureIncreased 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 ApproachesNew 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
ConclusionConclusion
Proper use of clinical prediction rules aids in better Proper use of clinical prediction rules aids in better utilization of imaging studies and cost effectivenessutilization of imaging studies and cost effectiveness
MDCT-PA is preferred diagnostic techniqueMDCT-PA is preferred diagnostic technique V/Q scan for patients with contraindication to iodine V/Q scan for patients with contraindication to iodine
contrastcontrast Low-dose CT-PA or reduced-dose lung Low-dose CT-PA or reduced-dose lung
scintigraphy in pregnancyscintigraphy in pregnancy Dual energy CT can depict regional perfusion Dual energy CT can depict regional perfusion
status as well as intravascular embolistatus as well as intravascular emboli High pitch low dose technique can reduce motion High pitch low dose technique can reduce motion
artifactsartifacts
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