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The Left Ventricle: How Should We Quantify Its Size and Function; Is It Time for 3D in Everyone? Roberto M Lang, MD Conflict of Interests Philips Medical Imaging Research Grants Speakers bureau Advisory bureau Tomtec Research Grants Epsilon Research Grants 1

Eye ball How do we Assess LV Function? Qualitative Assessment Subjective Experience dependent Lack of standardization Large inter- and intraobserver variability J AM Soc Echocardiogr 2005; 18:1440-1463 2

Left Ventricular Volumetric Measurement 1 Biplane Disk Summation Area Length Method 2 Quantitation of 2D Echocardiography: 2016 Hand tracing Correct view? Foreshortening? Correct shape? Geometry dependent? Tracing errors? Correct trace? 3

Cardiac Chamber Quantification: What is New? Database Deformation Imaging RT3DE Eur Heart J Cardiovasc Imaging. 2015 Mar;16(3):233-71. J Am Soc Echocardiogr 2015;28:1-39 4

Chamber Quantification Uses of 3D Echocardiography Recommended Promising Clinical Trials Areas of active Research LV Volumes LV Mass LV Shape MV anatomy RV Volumes LV Dyssynchrony MV Stenosis Ao Anatomy LA Volumes Guidance of Transcatheter Procedures Ao Stenosis MV Regurgitation Prosthetic Valves Lang RM, Badano L et al, JASE 2012 5

Why is 3D More Accurate? long axis (cm) 11 10 9 8 A4C * 7 2D 3D Mor-Avi V, Lang RM et al., Circulation 2004. 110: 1814-1818. 3 6

Validation by MRI Improved accuracy: validation against CMR EDV, ESV Excellent correlation (r²>0.85) but RT3DE underestimates volumes Jacobs LD, et al. Eur Heart J 2005; 27:460-8 Sugeng L, et al. Circulation 2006; EUROECHO 114:654-61 2009 - Madrid Jenkins C, et al. J Am Soc Echocardiogr 2007; 20:962-8 Soliman OI, et al. Am Soc Echocardiogr 2007; 20:1042-9 Sources of error: 3D Egg-shaped phantom Small difference between the 2 boundaries resulted in an 11% difference in the measured volume of the 3D shell! Mor-Avi V.,Lang RM et al, JACC Cardiovasc Img 2008: 1: 413-423 7

LV Volumes: 3DE Advantages Avoid image foreshortening No geometric assumptions More accurate and reproducible Disadvantages Low temporal resolution Less data on normals Limitations to the Implementation of 3D Echocardiography in the Laboratory Time-consuming Requires training in 3DE analysis Accuracy varies with expertise Reproducibility varies among EUROECHO 2009 - Madrid individuals and institutions 8

Real-Time Automated 3D TTE Left Heart Chamber Quantification using an Adaptive Analytics Algorithm Automated Model-Based Segmentation of the Heart CT MRI 3DE TIME 3 9

Real-Time Automated Transthoracic Three- Dimensional Echocardiographic Left Heart Chamber Heart Quantification Model Overview using an Adaptive Analytics Algorithm Generic Model Final Model Tsang w, Lang RM. JACC Imaging (in press) Library of ~1000 Images Local Adaptation Adjustments for: variations in dropout acoustic clutter ventricular shape dataset orientation Real-Time Automated Transthoracic Three- Dimensional Echocardiographic Left Heart Chamber Quantification using an Adaptive Analytics Algorithm Dilated Banana Sigmoid Septum Normal Tsang w, Lang RM. JACC Imaging (in press) 10

Real-Time Automated Transthoracic Three-Dimensional Echocardiographic Left Heart HeartModel A.I. Chamber Quantification using an Adaptive Analytics Algorithm Algorithm Align & Orient Model Adjust Local Borders Automatically Corrects Foreshortening Avoids Geometric Assumptions 15 Initial fully automated model Global/regional corrections LV Focused Views Final model 4-chamber 2-chamber 3-chamber LA Focused Views 11

A LV Focused Views 4-chamber 2-chamber 3-chamber B LA Focused Views C 4-chamber 2-chamber 3-chamber Fully Automated Cardiac Chamber Quantification 3D RV End- Diastolic Volume 3D LV End- Diastolic Volume 3D RV End- Systolic Volume 3D RV Ejection Fraction 3D RA Volume at LV End-Systole EUROECHO 2009 - Madrid 3D LV End- Systolic Volume 3D LV Ejection Fraction 3D LA Volume at LV End- Systole Tsang w, Lang RM. JACC Imaging (in press) 12

Time Savings 2h and 56 min 63% 1h and 6 min 82% 33 min EUROECHO 2009 - Madrid Uses of 3D Echocardiography Recommended Promising Clinical Trials Areas of active Research LV Volumes LV Mass LV Shape MV anatomy RV Volumes LV Dyssynchrony MV Stenosis Ao Anatomy LA Volumes Guidance of Transcatheter Procedures Ao Stenosis MV Regurgitation Prosthetic Valves Lang RM, Badano L et al, JASE 2012 13

LV Remodeling LV SHAPE LV Function 27 Pre-Operative 6 Months 12 Months Pre-operative 6 months 12 months Maffessanti F, Caiani EG, Tamborini G, Muratori M, Sugeng L, Weinert L, Alamanni F, Zanobini M, Mor-Avi V, Lang RM, Pepi M. Am J Cardiol 2010 September 15;106(6):836-842. 14

2D Sphericity Index 2DE Si = Biplane EDV Volume of sphere with the *100 LV long axis as diameter [Marsan et al, Ann Thorac Surg 2011;91:113-22] Application to 2D echocardiographic images, LV EDV was obtained by apical biplane Simpson s rule, to study in men the pathogenesis of MR. [Van Dantzig et al, Am Heart J 1996;131;865] LV sphericity (%) MR 0-2 MR 3-4 33±8 41±8* Increased LV sphericity associated with severity of MR, independent of LV volumes. 3D Sphericity Index 3D dataset reconstructed from multiple 2D echo apical freehand acquisitions SI V 3D LVV 3 4 D 3 2 [Mannaerts et al. Eur Heart J 2004;25:680-7] Unlike the traditional 2D indices, the 3D sphericity index can predict, accurately and soon in the sub-acute phase after AMI, which patient is likely to undergo LV remodeling. 15

LV shape LV volume 2/20/2017 New shape indexes based on LV Contour Application to LV surfaces extracted from RT3DE:.5 s( ) s norm 0 index norm 1 A A max A max Reference shape signal was defined from LV moments of inertia (I X, I Y, I Z ) Shape index: degree of similarity between LV and a reference shape Two shape indices: sphericity S and conicity C A 1 [Maffessanti et al, Ultrasound Med Biol 2009;35:1953-62] New shape indexes based on LV Contour Evolution through the cardiac cycle in a normal subject ES ES time Normal subject, 36 yrs time 16

LV Shape: Regional Curvature Salgo, Tsang, Lang et al. JASE 2011: 25(1):80-8 Basic IDEA EUROECHO 2009 - Madrid 34 17

Curvature: the amount by which k =1/r a geometric object deviates from being flat. A Circ 1980;61:626-33] 1 k1 R 1 1 k2 R 2 k =1/r R 1 3D Curvature Segmentation 3D RV Shape in Pressure overload 36 18

LV Shape Analysis Salgo I, Tsang W, Lang RM et al., J Am Soc Echocardiogr 2011: 25(1):80-8 19

LV SEPTAL & APICAL REMODELING Salgo I, Tsang W, Lang RM et al., J Am Soc Echocardiogr 2011: 25(1):80-8 Salgo, Tsang, Lang et al. JASE 2011: 25(1):80-8 20

3D Regional LV Remodeling: A New Prognosticator of Outcomes in NIDCM M. Cristina Abduch, Ivan Salgo, Wilson Mathias, Roberto Lang RV Shape: Regional Curvature 0.6 R 1 0.5 0.4 0.3 0.2 0.1 0.0-0.1-0.2 Normalized Curvature k n Curvature < 0 Curvature > 0 Curvature = 0 Convexity Concavity 21

Free wall surface Septal wall surface 2/20/2017 Normal RV Shape PAH Normal 1.5 1.0 0.5 0.0 Indexed Curvature -0.5 1.5 1.0 0.5 0.0 Indexed Curvature -0.5 22

LVAD Thoratec HeartMate II Ascending aorta Outflow cannula Left ventricle Inflow cannula 3D CT reconstruction RAMP Study 3D analysis 76mm 8000 ED 69mm 8400 ES 8800 9600 10000 10400 10800 11200 Increasing LVAD speed (in rpm) 23

LV Endocardial surfaces in LVAD RPM = 8000 RPM = 9600 RPM = 10800 Radius (mm) LV Endocardial surfaces in LVAD 24

Multiple images from a patient are registered and overlaid or merged Fused images may be created from multiple images from the same imaging modality, or by combining information from multiple modalities, such as MRI, CT, PET and SPECT. U N I V E R S I T Y O F C H I C A G O N O N - I N V A S I V E C A R D I A C I M A G I N G L A B O R A T O R Y Software Image registration Spatial compounding Mosaicing (Stitching) U N I V E R S I T Y O F C H I C A G O N O N - I N V A S I V E C A R D I A C I M A G I N G L A B O R A T O R Y 25

HYBRID SYSTEM SPECT-CT fusion imaging integrating anatomy and perfusion O. Gaemperli; et al European Heart Journal Vol 28, N o 2, January 200. U N I V E R S I T Y O F C H I C A G O N O N - I N V A S I V E C A R D I A C I M A G I N G L A B O R A T O R Y 26

Anterior view Lateral view 2/20/2017 Longitudinal Circumferential Radial 27

Stress CT perfusion Resting longitudinal strain 2/20/2017 90 <50% LAD stenosis >70% RCA stenosis 75 60 50 Antero-septal view Antero-lateral view Infero-septal view 5-5 -15-25 Software Image registration Spatial compounding Mosaicing (Stitching) U N I V E R S I T Y O F C H I C A G O N O N - I N V A S I V E C A R D I A C I M A G I N G L A B O R A T O R Y 28

Grau et al [IEEE Trans Med Imaging 2007;26:1154-65]: extension to the combination of parasternal and apical RT3DE datasets. To combine multiple ultrasound images obtained from different transducer positions to improve the quality of the compounded image. Rajpoot et al [Med Imaging Analysis 2009;134-143]: combination of multiple apical RT3DE datasets. Yao et al [Phys Med Biol 2011;56:6109] : compounding of up to 10 datasets U N I V E R S I T Y O F C H I C A G O N O N - I N V A S I V E C A R D I A C I M A G I N G L A B O R A T O R Y Software Image registration Spatial compounding Mosaicing (Stitching) U N I V E R S I T Y O F C H I C A G O N O N - I N V A S I V E C A R D I A C I M A G I N G L A B O R A T O R Y 29

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Promises and Perspectives 3D Chamber Quantification, LV &RV Shape and Image Fusion Where have we been? Where are we going? Feasible Improved accuracy Improved reproducibility Mechanistic insights Improved temporal and spatial resolution Improved integration into clinical practice Automation Establish outcome measures/guidelines Decreased costs 31

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