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euroecho2010-contrast-echo-cosyns-629 by qingyunliuliu

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									Contrast echo current applications

  Pr B Cosyns (UZ Brussels - CHIREC, BE)



                No Disclosure



               EUROECHO CONGRESS - COPENHAGEN -
                     TEACHING COURSE 2010
               Overview

•   Bubbles physics, pharmacology
•   Imaging instrumentation for contrast
•                        g
    Available contrast agents
•   Current clinical applications
•   S f t issues
    Safety i
•   EAE recommendations


                EUROECHO CONGRESS - COPENHAGEN -
                      TEACHING COURSE 2010
               Overview

•   Bubbles physics, pharmacology
•   Imaging instrumentation for contrast
•                        g
    Available contrast agents
•   Current clinical applications
•   S f t issues
    Safety i
•   EAE recommendations


                EUROECHO CONGRESS - COPENHAGEN -
                      TEACHING COURSE 2010
Contrast agents for echocardiography

             • size: 1- 8 μ
             • biodegradable
             • scatter US



              Shell:
              • protein
              • lipid
              • surfactant
  • air       • polymer
  • gas
  • liquid
    Contrast echo:How it works




ƒ



                    ƒ

                        ƒ2
                             ƒ4
                                  ƒ6
Example of left ventricular
           ifi ti
     opacification
Myocardial Perfusion
Micro-bubbles and Ultrasound




                               Mechanical
                                 Index
The destruction-replenishment principle


           A.   B.    C.   D.        E




                                {
                           {
                      {
                {



     E           d1   d2   d3   d4

    time   0     t1   t2   t3   t4
Example of normal myocardial
         perfusion
    Q                  y
    Quantification of Myocardial Blood Flow
                                  VI
       A
       A.   B
            B.    C.
                  C    D.
                       D     E              (1 e βt
                                       y= A (1-e-βt )                     A



                                          l
                                       ß slope




                            {
                       {
                  {
            {




E            d1   d2   d3   d4
                                                          Time interval
time   0     t1   t2   t3   t4   ß= microbubble velocity
                                                  cross sect.
                                 A= microvascular cross. sect area




                                                                              473-
                                              Wei et al. Circulation 1998;97; 473- 83
               Overview

•   Bubbles physics, pharmacology
•   Imaging instrumentation for contrast
•                        g
    Available contrast agents
•   Current clinical applications
•   S f t issues
    Safety i
•   EAE recommendations


                EUROECHO CONGRESS - COPENHAGEN -
                      TEACHING COURSE 2010
    Specific Imaging Techniques
             Real-
             Real-time high MI imaging



        Hz
FR = 30 H              Every 33 msec μb will
                           be destroyed

                                               Replenishment
                5 mm = elevation beam           never occurs


  Cap               RBC vel= 1mm / s = 0.033mm / 33 msec
           p          g g        q
          Specific Imaging Techniques
•   High Power Techniques – Intermittent Imaging Triggered harmonic
    imaging
    i    i

•   Harmonic Power Doppler

•   Pulse Inversion Doppler

•   Ultraharmonic imaging

•                   q                   g g
    Low Power Techniques – Real Time Imaging

•   Power pulse inversion imaging

•   Power modulation imaging
High Power Intermittent Imaging




 40 msec      80 msec      200 msec                  500 msec




1,000 msec   5,000 msec   10,000 msec               30,000 msec




                                Van Camp AHA 2001
Power Doppler Technology
Pulse Inversion Technique
            Power Modulation
 Transmit                      Receive


Half




Full
            Power Modulation
 Transmit                             Display
               Bubbles : Non linear

Half

                    2


Full
               Substract =
            Power Modulation
 Transmit                                   Display
             Tissue: Linear / Suppression

Half

                      2


Full
                 Substract =
               Overview

•   Bubbles physics, pharmacology
•   Imaging instrumentation for contrast
•                        g
    Available contrast agents
•   Current clinical applications
•   S f t issues
    Safety i
•   EAE recommendations


                EUROECHO CONGRESS - COPENHAGEN -
                      TEACHING COURSE 2010
Available contrast agents




                            2
                            3
               Overview

•   Bubbles physics, pharmacology
•   Imaging instrumentation for contrast
•                        g
    Available contrast agents
•   Current clinical applications
•   S f t issues
    Safety i
•   EAE recommendations


                EUROECHO CONGRESS - COPENHAGEN -
                      TEACHING COURSE 2010
      Current Clinical Applications

• Endocardial border delineation
  – At rest
  – During stress test
• Doppler signal enhancement
• Tissue characterization
• Myocardial perfusion
  – At rest
  – During stress


                    EUROECHO CONGRESS - COPENHAGEN -
                          TEACHING COURSE 2010
    Endocardial border delineation


• 5-10 % of echocardiographic examinations
  : poor quality imaging

• Decrease the need for expertise

• Accurate quantification of LV (>CMR)



                      Malm Am Coll Cardiol 2004;44:1030-5.
                      M l J A C ll C di l 2004 44 1030 5

               EUROECHO CONGRESS - COPENHAGEN -
                     TEACHING COURSE 2010
Endocardial border delineation : 3DE




                                 Cosyns CV ultrasound 2009

            EUROECHO CONGRESS - COPENHAGEN -
                  TEACHING COURSE 2010
Endocardial border delineation : 3DE




                                     Jenkins EHJ 2009

            EUROECHO CONGRESS - COPENHAGEN -
                  TEACHING COURSE 2010
                         Stress protocol

Dobutamine (µg/kg/min)                                (Atropine)

                                                      40
                                         30
                             20
                10
     0
                     Contrast Infusion




                         Wall motion analysis (ASE)
Stress Contrast




         Plana J Am Coll Cardiol Imaging 2009.
Stress Contrast




         Plana J Am Coll Cardiol Imaging 2009.
Doppler signal enhancement


         •   75 years old Man

         •   Hx f
             H of COPD

         •   Admitted for severe dyspnea

         •   Murmur at the auscultation 3/6

         •   Echocardio: poor quality




        EUROECHO CONGRESS - COPENHAGEN -
              TEACHING COURSE 2010
Doppler signal enhancement


         •   75 years old Man

         •   Hx f
             H of COPD

         •   Admitted for severe dyspnea

         •   Murmur at the auscultation 3/6

         •   Echocardio with contrast : AS




        EUROECHO CONGRESS - COPENHAGEN -
              TEACHING COURSE 2010
Tissue characterization




      EUROECHO CONGRESS - COPENHAGEN -
            TEACHING COURSE 2010
             Tissue characterization




             d1




                                 End-Systole
Thickness of the compacted layer ( C ) and the non-compacted ( N ) layer of the
 endocardium is taken at the maximal thickness with a ratio N/C > 2 in PSAX




                                          Jenni et al Heart 2001 86: 666-671
Tissue characterization




       EUROECHO CONGRESS - COPENHAGEN -
             TEACHING COURSE 2010
Myocardial perfusion




     EUROECHO CONGRESS - COPENHAGEN -
           TEACHING COURSE 2010
                Myocardial perfusion
MCE can define area at risk

MCE can define collateral circulation to the infarct‐related artery in 
nonreperfused AMI

MCE perfusion patterns give more complete information about restoration 
of flow at the microcirculation level compared to invasive techniques

MCE allows the diagnosis of no‐reflow and allows the evaluation of 
dynamic changes of myocardial perfusion after reflow

MCE showing no‐reflow has prognostic importance: less LV systolic 
function recovery, adverse LV remodeling, more complications
function recovery, adverse LV remodeling, more complications




                          EUROECHO CONGRESS - COPENHAGEN -
                                TEACHING COURSE 2010
               Myocardial perfusion

56 years old woman

Acute typical chest pain
 cu e yp ca c es pa

ECG normal

Waiting for troponin

Echo : WMA ?




                               Tsutsui, Echocardiography 2005; 22: 487-495
                           EUROECHO CONGRESS - COPENHAGEN -
                                 TEACHING COURSE 2010
Myocardial perfusion : stress
    F             1beat             5 beats




         EUROECHO CONGRESS - COPENHAGEN -
               TEACHING COURSE 2010
Myocardial perfusion




                          Senior , EJE 2009
    EUROECHO CONGRESS - COPENHAGEN -
          TEACHING COURSE 2010
               Overview

•   Bubbles physics, pharmacology
•   Imaging instrumentation for contrast
•                        g
    Available contrast agents
•   Current clinical applications
•   S f t issues
    Safety i
•   EAE recommendations


                EUROECHO CONGRESS - COPENHAGEN -
                      TEACHING COURSE 2010
Safety in Clinical Practice
    Potential side effects of UCA


• Pseudo complications

• Anaphylactoid reactions

  Bioeffects
• Bi ff t
    Anaphylactoid reactions with UCA (1)
•   Hypersenstivity nonIGE mediated, complement activation and
    thromboxane release

•   Does not required prior sensitization

•   Frequent with liposomal drugs (7%)

•   Associated with palmar erythema and back pain

•   Severe forms:
     – Hypotension
     – Bronchospasm
     – Hypoxemia
     – (Seizures, seizures-like reactions, altered consciousness ?)
    Anaphylactoid reactions with UCA (2)

•   Lipid particles: C activation related pseudo allergy like syndrome
    (CARPA)
•   CARPA influenced by :
     – Surface charge
     – Lipid dose
     – Size (surface area)
                     non ionic                     (polaxamer
     – Presence of non-ionic polymer at surface (polaxamer, PEG)
     – Pre formed anti-lipid antibodies
•   All MBB may have potential of C activation at their surface
•   CARPA 1/10000

•               p   p     ,         g      ,                   g
    Treatment: epinephrine, beta 2 agonists, antihistaminic drugs and
    methylprednisone 125 mg for late reaction
                   UCA bioeffects (1)

•   Time varying pressure and microcavitation

•   Generate:
       Heat
     – H t
     – Shear stess
     – Oxygen radicals
     – Hemolysis

•   May induce:
     – Sonoporation
     – Capillary rupture
     – Erythocyte extravasation
     – Endothelial cell damage
                      UCA bioeffects (2)
•   Dose dependency

•   Related to
     – Shell composition
     – Frequency of insonification
     – Power of the ultrasound beam
     – Duration of exposure

•   In   animals induce:
     –    Transient decrease in LV sustolic function
     –    Aggregation
     –    Coalescence
     –    Lodging
     –    Ventricular arrhthmias
     –    Microvascular injury
    Clinical significance of UCA bioeffects

•   PVC’s (controversial)

•                                        necrosis
    No relevant increase in biomarker of necrosis, inflammation and
    oxydative stress

•   Increase in arteriovenous gradient of troponin I
    I        i    t i            di t f t       i

•   No subclinical dysfunction with TDI

•   Retrospective studies no clinical evidence
           g
Clinical significance of UCA bioeffects




                         Kawaja AJC 2010
     Relevance of potential side effects


•   To be able to recognize and to treat hypersensitvity reactions

•   Monitoring in patients with PHT or unstable cardiopulmonary
    conditions

•   Use of the minimal dose of contrast (diluted, pump rather than
    bolus,…)

•   Low MI as possible (<1.0)
               Overview

•   Bubbles physics, pharmacology
•   Imaging instrumentation for contrast
•                        g
    Available contrast agents
•   Current clinical applications
•   S f t issues
    Safety i
•   EAE recommendations


                EUROECHO CONGRESS - COPENHAGEN -
                      TEACHING COURSE 2010
EAE recommendations




     EUROECHO CONGRESS - COPENHAGEN -
           TEACHING COURSE 2010
EAE recommendations




     EUROECHO CONGRESS - COPENHAGEN -
           TEACHING COURSE 2010
EAE recommendations




     EUROECHO CONGRESS - COPENHAGEN -
           TEACHING COURSE 2010
EAE recommendations




     EUROECHO CONGRESS - COPENHAGEN -
           TEACHING COURSE 2010
                    Conclusions

• Contrast echocardiography should be used:
  – To enhance endocardial border delineation at rest or
    during stress
  – To better characterize tissue (thrombus,
    cardiomyopathies,…)
  – To enhance Doppler signal
  – To assess perfusion (requires some expertise and
    specific equipment)


                           q
• Contrast is a safe technique



                     EUROECHO CONGRESS - COPENHAGEN -
                           TEACHING COURSE 2010
EUROECHO CONGRESS - COPENHAGEN -
      TEACHING COURSE 2010
                         Sonovue (1)
•   BR1

•   Sulfur hexafluoride gas

•   Phospholipid shell

•   Shell:
     – Macrogel 4000 (=PEG) (osmotic laxative, long linear polymer).
       This is known to be associated with the occurrence of allergic
       reactions (Van Camp, 2007)
     – Distearoylfosfatidylcholine
       Dipalmitoylfosfatidylglycerol natrium
     – Di l i     lf f id l l      l     i
     – Palmitinezuur
                         Sonovue (2)
•   2 – 5 x 108 µB/ml

•   1 a 10 µm (>90% < 6 µm; > 90% secondary to MBB between 2 a
      µ )(          ,     )
    8 µm) (Schneider, 2002)

•   Seems to be selectively taken up in the spleen, while within the
               kidneys,
    liver and kidneys the microbubbles are purely a vascular agent
    with no evidence of selective uptake (Lim, 2004)
      – Phagocytosed by macrophages?
        Trapped ithin               pa ench ma?
      – T apped within the splenic parenchyma?
      – Behavior of SonoVue analogous to that of the heat-damaged
        red blood cells at nuclear imaging, which are higly spleen
             ifi   d        tt k       b th li       lik    ll id l b l d
        specific and are not taken up by the liver unlike colloid-labeled
        tracers?
                         Sonovue (3)

•   Stored in the form of dry lyophilized precursors: lipid is first
    intermixed with the water-soluble dry matrix, such as salt,
       b h d t              d    l d in    i l   t i i
    carbohydrate or PEG and sealed i a vial containing fl       i t d
                                                          fluorinated
    gas atmosphere.

•   Water is added to the vial immediately prior to use. It dissolves
    the matrix, but not the lipid shell, and microbubbles are generated
    in the form of aqueous dispersion. (Klibanov, 2009, Med Biol Eng
    Comput)

								
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