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Advances in Pulmonary Embolism Imaging

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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; ... – PowerPoint PPT presentation

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Title: Advances in Pulmonary Embolism Imaging


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

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.
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 141235.
  • Weinmann, EE Salzman, EW. N. Engl. J. Med. 1994
    3311630.

6
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
1082726-2729.
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)1386-9. Stein PD et al. Am. J.
Med. 2007 Oct120(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

Goldhaber SZ Visani L De Rosa M. Lancet 1999
Apr 24353(9162)1386-9. Stein PD et al. Am. J.
Med. 2007 Oct120(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 295172-179.
10
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 295172-179.
11
Modified Wells Criteria
  • Wells PS et al. Thromb Haemost 2000 Mar
    83(3)416-20.

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. 2004 Apr
    20140(8)589-602.
  • De Monye W et al. Am. J. Respir. Crit. Care Med.
    2002 Feb 1165(3)345-8.
  • Perrier et al. Am. J. Respir. Crit. Care Med.
    2003 16739-44.

13
The Christopher Study Workup Algorithm
Writing Group for the Christopher Study
Investigators JAMA. 2006 295172-179.
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

Turkstra F Kuijer PM van Beek EJ Brandjes DP
ten Cate JW Buller HR. Ann Intern Med. 1997 May
15126(10)775-81.
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

Anderson DR Barnes D. Semin. Nucl. Med. 2008
Nov38(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

Stein PD et al. N. Engl. J. Med. 2006 Jun
1354(22)2317-27.
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. 2004 Feb
    230329-337.

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. 2004 Feb
    230329-337.

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
  • Kluge, A. et al. Am. J. Roentgenol.
    2006187W7-W14

Stein PD et al. Ann Intern Med. 2010152434-43.
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 3361449.
  • Haage P et al. Am. J. Respir. Crit. Care Med.
    2003 Mar 1167(5)729-34. Epub 2002 Nov 21.
  • Spuentrup E et al. Am. J. Respir. Crit. Care Med.
    2005 Aug 15172(4)494-500. 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
The PIOPED Investigators. JAMA. 1990 May
23-30263(20)2753-9.
23
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. 2008246941-6.
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)
  • Anderson DR et al. JAMA. 2007 Dec
    19298(23)2743-53.
  • Sostman DH et al. Radiology. 2008 Jan
    14246941-946.

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. 2007 Jan24215-21.
  • Marik PE Plante LA. N. Engl. J. Med.
    20083592025-33.

26
Multidetector-CTTechnique
  • 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.
200515(4)d37-d41.
27
Multidetector-CTFindings
  • 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.
200324(4)271-231.
28
MDCT Findings
C
D
B
A
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.
200324(4)231-271.
31
Clinical relevance of MDCT findingsI.
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. 20064(4)724-731. Goodman LR.
Radiology. 2005234(3)654-658. Glassroth J. JAMA.
2007298(23)2788-2789.
32
Patient with pneumonectomy
Lingular subsegmental pulmonary embolism (arrow)
33
Clinical Relevance of MDCT findings II. RV Strain
  • Increased RVLV ratio correlated with increased
    thrombus load
  • Increased RV diastolic dimensions on axial CT
    correlate with worse outcome in acute PE

Massive bilateral PE with signs of RV strain.
Dilated RV with visible thrombus (arrow).
Sanchez O et al. Eur. Heart J. 200829156977.
34
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

36
Clinical Relevance of MDCT findingsiv. 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

Massive PE with RV strain and mosaic attenuation
(arrow)
Wittram C et al. AJR 2006186S421-S429.
37
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38
Diagnostic Imaging Algorithm
Adapted from Agnelli G Becattini C. N. Engl. J.
Med. 2010363266-74.
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. 200815(12)1494.
40
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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
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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. 2010363266-74.
  • 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 19298(23)2743-53.
  • Anderson DR Barnes D. The use of leg venous
    ultrasonography for the diagnosis of pulmonary
    embolism. Semin. Nucl. Med. 2008 Nov38(6)412-7.
  • Carson JL Kelly MA Duff A, et al. The clinical
    course of pulmonary embolism. N Engl J Med 1992
    May 7326(19)1240-5.
  • Chatellier G et al. Prognostic value of right
    ventricular dysfunction in patients with
    haemodynamically stable pulmonary embolism a
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  • 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
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    Med. 2002 Feb 1165(3)345-8.
  • Glassroth J. Imaging of Pulmonary Embolism Too
    much of a Good Thing? JAMA. 2007298(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
    24353(9162)1386-9.
  • Goldhaber Z Elliot CG. Acute Pulmonary Embolism
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  • Goodman LR. Small pulmonary emboli what do we
    know? Radiology. 2005234(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
    1167(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
    Jul163(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. 2006187W7-W14.
  • Le Gal G Righini M Parent F Van Strijens M
    Couturaud F. Diagnosis and management of
    subsegmental pulmonary embolism. J. Thromb
    Haemost 20064(4)724-731.
  • Macdonald S Mayo J. Computed Tomography of Acute
    Pulmonary Embolism. Semin. Ultrasound CT.
    200324(4)271-231.
  • Marik PE Plante LA. Venous thromboembolic
    disease and pregnancy. N. Engl. J. Med.
    20083592025-33.
  • Moser KM. Venous thromboembolism. Am. Rev.
    Respir. Dis. 1990141235.
  • Nakos G Kitsiouli EI Lekka ME. Bronchoalveolar
    lavage alterations in pulmonary embolism. Am. J.
    Respir. Crit. Care Med. 1998 Nov158(5 Pt
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  • Perrier et al. Cost-Effectiveness Analysis of
    Diagnostic Strategies for Suspected Pulmonary
    Embolism Including Helical Computed Tomography.
    Am. J. Respir. Crit. Care Med. 200316739-44.

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. 200515(4)d37-d41.
  • Schoepf J Costello P. CT Angiography for
    Diagnosis of Pulmonary Embolism State of the
    Art. Radiology. 2004 Feb230329-337.
  • Sostman DH et al. Acute Pulmonary Embolism
    Sensitivity and Specificity of Ventilation-Perfusi
    on Scintigraphy in PIOPED II Study. Radiology.
    2008 Jan 14246941-946.
  • Sostman HD Stein PD Gottschalk A Matta F Hull
    R Goodman L. Acute pulmonary embolism
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    on scintigraphy in PIOPED II study. Radiology.
    2008246941-6.
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    Botnar RM Mahnken AH Gunther RW Buecker A.
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    15172(4)494-500. Epub 2005 Jun 3.
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    Pathways in Acute Pulmonary Embolism
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  • Stein PD Beemath A Matta F Weg JG Yusen RD
    Hales CA Hull RD Leeper KV Jr Sostman HD
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    Wakefied TW Woodard PK. Clinical characteristics
    of patients with acute pulmonary embolism data
    from PIOPED II. Am. J. Med. 2007
    Oct120(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.
    2010152434-43.
  • Stein PD Fowler SE Goodman LR Gottschalk A
    Hales CA Hull RD Leeper KV Jr Popovich J Jr
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    Wakefield TW Weg JG Woodard PK. Multidetector
    computed tomography for acute pulmonary embolism.
    N. Engl. J. Med. 2006 Jun 1354(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 20140(8)589-602.
  • Subramaniam, RM et al. Pulmonary Embolism
    Outcome A Prospective Evaluation of CT Pulmonary
    Angiographic Clot Burden Score and ECG Score. Am.
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    approaches. N. Engl. J. Med. 19973361449.
  • 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 23-30263(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 15126(10)775-81.
  • Weinmann EE Salzman EW. Deep-vein thrombosis. N.
    Engl. J. Med. 19943311630.
  • 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 Mar83(3)416-20.
  • Wittram C et al. Acute and Chronic Pulmonary
    Emboli AngiographyCT Correlation. AJR
    2006186S421-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. 2006295172-179.
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