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
Clinical symptoms of DVT (leg swelling, pain with palpation) 3.0
Other diagnosis less likely than PE 3.0
Heart rate gt100 1.5
Immobilization or surgery in previous 4 weeks 1.5
Previous DVT/PE 1.5
Hemoptysis 1.0
Malignancy 1.0
PE Likely gt4
PE Unlikely lt/ 4

• 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
Scan Probability Clinical Probability of Pulmonary Emboli Clinical Probability of Pulmonary Emboli Clinical Probability of Pulmonary Emboli
Scan Probability High Intermediate Low
High 95 86 56
Intermediate 66 28 15
Low 40 15 4
Normal or near normal 0 6 2
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.

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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.
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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
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  MV. Embolus location affects the sensitivity of a
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• 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
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  24353(9162)1386-9.
• Goldhaber Z Elliot CG. Acute Pulmonary Embolism
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  Diagnosis. Circulation 20031082726-2729.
• 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
  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. 200316739-44.

45
References

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  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
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• Spuentrup E Katoh M Wiethoff AJ Parsons EC Jr
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  J. Respir. Crit. Care Med. 2005 Aug
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• Stein P Woodard P Weg J, et al. Diagnostic
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  Radiology. 2007 Jan24215-21.
• 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
  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
  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 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.
  J. Roentgenol. 20081901599-1604.
• Tapson VF. Pulmonary embolism new diagnostic
  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.