Ebook Essential echocardiography - A companion to braunwald’s heart disease: Part 1

Part 1 book “Essential echocardiography - A companion to braunwald’s heart disease” has contents: Physical principles of ultrasound and generation of images, M-mode imaging, principles of contrast echocardiography, principles of transesophageal echocardiography, principles of three-dimensional ultrasound,… and other contents.

ESSENTIAL

ECHOCARDIOGRAPHY

A Companion to Braunwald’s Heart Disease

The Edward D Frohlich Distinguished Chair

Professor of Medicine, Harvard Medical School Director

Director, Noninvasive Cardiology

Brigham and Women’s Hospital

Boston, Massachusetts

Assistant Professor of Medicine

Co-Director, Noninvasive Cardiology

Brigham and Women’s Hospital

Boston, Massachusetts

Dorothy and Lloyd Huck Chair

Department of Cardiovascular Medicine

Medical Director, Cardiovascular Service Line

Morristown Medical Center/Atlantic Health System

Morristown, New Jersey

Professor of Medicine

Sidney Kimmel Medical College

Thomas Jefferson University

Philadelphia, Pennsylvania

Illustration Editor

Noninvasive Cardiovascular Research

Cardiovascular Division

Brigham and Women’s Hospital

Boston, Massachusetts

1600 John F Kennedy Blvd.

Ste 1800

Philadelphia, PA 19103-2899

Copyright © 2019 by Elsevier, Inc All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions poli-cies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing

This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein)

Notices

Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a profes-sional responsibility

With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered,

to verify the recommended dose or formula, the method and duration of administration, and contraindications

It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions

To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any ity for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise,

liabil-or from any use liabil-or operation of any methods, products, instructions, liabil-or ideas contained in the material herein

Library of Congress Cataloging-in-Publication Data

Names: Solomon, Scott D., editor | Wu, Justina C., editor | Gillam, Linda

D., editor

Title: Essential echocardiography : a companion to Braunwald’s Heart disease

/ [edited by] Scott D Solomon, Justina C Wu, Linda D Gillam ;

illustration editor, Bernard E Bulwer

Other titles: Essential echocardiography (2019) | Complemented by

(expression): Braunwald’s heart disease 10th edition

Description: Philadelphia, PA : Elsevier, [2019] | Complemented by:

Braunwald’s heart disease / edited by Douglas L Mann, Douglas P Zipes,

Peter Libby, Robert O Bonow, Eugene Braunwald 10th edition 2015 |

Includes bibliographical references and index

Identifiers: LCCN 2017045233 | ISBN 9780323392266 (pbk : alk paper)

Subjects: | MESH: Echocardiography

Classification: LCC RC683.5.E5 | NLM WG 141.5.E2 | DDC 616.1/207543 dc23 LC record

Executive Content Strategist: Dolores Meloni

Senior Content Development Specialist: Rae Robertson

Publishing Services Manager: Catherine Jackson

Project Manager: Tara Delaney

Design Direction: Renee Duenow

Printed in China

To Caren, Will, Katie, and Dan

University of California at San Francisco

San Francisco, California

Vikram Agarwal, MD, MPH

Noninvasive Cardiovascular Imaging Program

Department of Medicine (Cardiology) and Radiology

Brigham and Women’s Hospital

Boston, Massachusetts

Lillian Aldaia, MD

Department of Cardiovascular Medicine

Morristown Medical Center, Gagnon

Bernard E Bulwer, MD, FASE

Noninvasive Cardiovascular Research

Department for Cardiovascular Diseases

University of Zagreb School of Medicine

University Hospital Centre Zagreb

Division of Cardiovascular Medicine

Brigham and Women’s Hospital

Boston, Massachusetts

Patrycja Z Galazka, MD

Division of Cardiovascular MedicineBrigham and Women’s HospitalBoston, Massachusetts

Linda D Gillam, MD, MPH, FACC, FASE, FESC

Dorothy and Lloyd Huck ChairDepartment of Cardiovascular MedicineMedical Director, Cardiovascular Service LineMorristown Medical Center/Atlantic Health SystemMorristown, New Jersey

Professor of MedicineSidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphia, Pennsylvania

Alexandra Goncalves, MD, MMSc, PhD

Cardiovascular DivisionBrigham and Women’s HospitalBoston, MassachusettsDepartment of Physiology and Cardiothoracic SurgeryUniversity of Porto Medical School

Porto, Portugal

John Gorcsan III, MD

Professor of MedicineDirector of Clinical ResearchWashington University in St Louis

St Louis, Missouri

John D Groarke, MBBCh, MSc, MPH

Brigham and Women’s Hospital Heart and Vascular Center;

Cardio-Oncology ProgramDana-Farber Cancer Institute/Brigham and Women’s HospitalBoston, Massachusetts

Deepak K Gupta, MD

Assistant Professor of MedicineDivision of Cardiovascular MedicineVanderbilt Translational and Clinical Cardiovascular Research CenterVanderbilt University Medical Center

Nashville, Tennessee

Rebecca T Hahn, MD, FACC, FASE

Director of Interventional EchocardiographyCenter for Interventional and Vascular TherapyColumbia University Medical Center

New York, New York

Sheila M Hegde, MD

Cardiovascular DivisionBrigham and Women’s HospitalBoston, Massachusetts

Carolyn Y Ho, MD

Cardiovascular DivisionBrigham and Women’s HospitalBoston, Massachusetts

Morristown Medical Center

Morristown, New Jersey

Director, Healthcare Transformation Lab

Co-Director, Thoracic Aortic Center

Massachusetts General Hospital

Associate Professor of Medicine

Harvard Medical School

Cardiovascular Core Lab

Department of Cardiovascular Medicine

Morristown Medical Center

Morristown, New Jersey

André La Gerche, MBBS, PhD

Laboratory Head

Department of Sports Cardiology

Baker Heart and Diabetes Institute

M Lowell Edwards Professor of Cardiology

Knight Cardiovascular Institute and Oregon National

Prime Research Center

Oregon Health & Science University

Judy R Mangion, MD, FACC, FAHA, FASE

Associate Director of Echocardiography

Department of Cardiovascular Medicine

Brigham and Women’s Hospital

Boston, Massachusetts

Leo Marcoff, MD

Director of Interventional EchocardiographyDepartment of Cardiovascular MedicineMorristown Medical Center

Morristown, New JerseyAssistant Professor of MedicineSidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphia, Pennsylvania

Thomas H Marwick, MBBS, PhD, MPH

Director and Chief Executive, ProfessorBaker Heart and Diabetes InstituteMelbourne, Victoria, Australia

Federico Moccetti, MD

Oregon Health & Science UniversityPortland, Oregon

Cardiovascular DivisionUniversity Hospital BaselBasel, Switzerland

Monica Mukherjee, MD, MPH

Assistant Professor of MedicineDepartment of CardiologyJohns Hopkins UniversityBaltimore, Maryland

Faraz Pathan, MBBS

Imaging Cardiovascular FellowMenzies Institute for Medical ResearchHobart, Tasmania, Australia

Elke Platz, MD, MS

Assistant ProfessorDepartment of Emergency MedicineBrigham and Women’s HospitalHarvard Medical SchoolBoston, Massachusetts

Jose Rivero, MD, RDCS

Cardiovascular DepartmentBrigham and Women’s HospitalBoston, Massachusetts

Adult Congenital Heart Disease Cardiologist

Brigham and Women’s Hospital

Instructor

Boston Children’s Hospital

Harvard Medical School

Boston, Massachusetts

Amil M Shah, MD, MPH

Assistant Professor of Medicine

Harvard Medical School

Associate Physician

Division of Cardiovascular Medicine

Brigham and Women’s Hospital

Boston, Massachusetts

Douglas C Shook, MD, FASE

Chief, Division of Cardiac Anesthesia

Department of Anesthesiology, Perioperative and Pain Medicine

Brigham and Women’s Hospital, Harvard Medical School

Boston, Massachusetts

Scott D Solomon, MD

The Edward D Frohlich Distinguished Chair

Professor of Medicine, Harvard Medical School

Director, Noninvasive Cardiology

Brigham and Women’s Hospital

Boston, Massachusetts

Jordan B Strom, MD

Division of Cardiovascular Disease

Beth Israel Deaconess Medical Center

Eliza P Teo, MBBS

The Department of CardiologyRoyal Melbourne HospitalMelbourne, Australia

Seth Uretsky, MD, FACC

Medical Director of Cardiovascular ImagingDepartment of Cardiovascular MedicineMorristown Medical Center

Morristown, New JerseyProfessor of MedicineSidney Kimmel School of MedicineThomas Jefferson UniversityPhiladelphia, Pennsylvania

Rory B Weiner, MD

Inpatient Medical DoctorCardiology DivisionMassachusetts General Hospital;

Assistant Professor of MedicineHarvard Medical SchoolBoston, Massachusetts

Leah Wright, BAppSc

Baker Heart and Diabetes InstituteMelbourne, Victoria, Australia

Justina C Wu, MD, PhD

Assistant Professor of MedicineCo-Director, Noninvasive CardiologyBrigham and Women’s HospitalBoston, Massachusetts

Preface

Echocardiography, or cardiac ultrasound, is the most commonly used

imag-ing technique to visualize the heart and great vessels It remains an essential

tool for cardiovascular evaluation and management despite the emergence

of other imaging techniques such as cardiac magnetic resonance, computed

tomography, and nuclear imaging (SPECT and PET) Echocardiography

has proven diagnostic and prognostic value in the vast majority of

cardio-vascular diseases Compared to other techniques, it is relatively

noninva-sive, inexpennoninva-sive, and has none of the harmful effects of ionizing radiation

Because it is increasingly portable and available in virtually any clinical

set-ting, it may be used by a wide variety of practitioners, including

cardiolo-gists, intensivists, emergency physicians, anesthesiolocardiolo-gists, and others

The practice of echocardiography requires a strong knowledge of the

physical principles underlying ultrasound, an understanding of cardiac

anatomy and physiology, and an appreciation of the ultrasonic appearance

of both normal variants and different cardiovascular diseases Moreover,

echocardiography, at its core, is a hands-on technique in which obtaining

high-quality images is dependent on the skill and training of the operator

Essential Echocardiography: A Companion to Braunwald’s Heart Disease,

is designed as a textbook in echocardiography for anyone interested in

learning the technique, including practicing cardiologists, cardiology

fel-lows, sonographers, anesthesiologists, critical care physicians, emergency

physicians, radiologists, residents, and medical students The text is designed to be simple enough to serve as an introduction to the field, yet comprehensive enough to serve as a reference for experienced practi-tioners Written by expert echocardiographers and sonographers with an emphasis on the practical rather than the esoteric, the book focuses on the basic principles of anatomy, physiology, and the hands-on approaches necessary to acquire and interpret echocardiographic images with a rigor-ous focus on clinical care The abundant illustrations, most of which are also available on Expert Consult, underscore the importance of visual learning in echocardiography The images selected comprise an extensive collection of classic and clear examples, representing decades of experi-ence over multiple institutions and also recent advances in the field.Echocardiography remains a vital and evolving technology As a part

of the Heart Disease family, Essential Echocardiography will ensure that

students and practitioners of cardiology will have the tools and skills essary to apply ultrasonic imaging to the care of cardiac patients

nec-Scott D Solomon, MD Justina C Wu, MD, PhD Linda D Gillam, MD, MPH, FACC, FASE, FESC

Eugene Braunwald, MD

ANTMAN AND SABATINE

Cardiovascular Therapeutics

DE LEMOS AND OMLAND

Chronic Coronary Artery Disease

ISSA, MILLER, AND ZIPES

Clinical Arrhythmology and Electrophysiology

Diabetes in Cardiovascular Disease

MANN AND FELKER

Heart Failure

BAKRIS AND SORRENTINO

Hypertension

KORMOS AND MILLER

Mechanical Circulatory Support

MORROW

Myocardial Infarction

BRAUNWALD’S HEART DISEASE REVIEW AND ASSESSMENT

BLUMENTHAL, FOODY, AND WONG

Preventative Cardiology

OTTO AND BONOW

Valvular Heart Disease

CREAGER, BECKMAN, AND LOSCALZO

Vascular Medicine

LILLY

Braunwald’s Heart Disease

KRAMER AND HUNDLEY

Atlas of Cardiovascular Magnetic Resonance Imaging

ISKANDRIAN AND GARCIA

Atlas of Nuclear Cardiology

INTRODUCTION

Ultrasound imaging is ubiquitous in medical practice and is used to image

all regions of the body, including soft tissues, blood vessels, and muscles

The machines used for ultrasound imaging range from small hand-held

ultrasound devices no bigger than a smartphone to more elaborate and

complex systems capable of advanced imaging techniques such as

three-dimensional (3D) imaging Although imaging of the heart and great vessels

has traditionally been referred to as “echocardiography,” the

fundamen-tal physical principles of image generation are common to all ultrasound

devices These principles should be familiar to the end-user because they

are essential to understanding the utility and limitations of ultrasound and

to the interpretation of ultrasound images and can help optimize the use of

ultrasound systems to obtain the highest-quality images

GENERATION OF IMAGES BY ULTRASOUND

The generation of images by ultrasound is based on the pulse-echo

prin-ciple.1-3 It is initiated by an electric pulse that leads to the deformation of

a piezoelectric crystal housed in a transducer This deformation results in

a high-frequency (>1,000,000 Hz) sound wave (ultrasound), which can

propagate through a tissue when the transducer is applied, resulting in an

acoustic compression wave that will propagate away from the crystal through

the soft tissue at a speed of approximately 1530 m/s As with all sound

waves, each compression is succeeded by decompression: the rate of these

events defines the frequency of the wave In diagnostic ultrasound imaging,

this applied frequency is generally between 2.5 and 10 MHz, which is far

beyond the level audible by humans, and is thus termed ultrasound.

The principal determinants of the ultrasound wave are: (1) wavelength

(λ), which represents the spatial distance between two compressions

(and is the primary determinant of axial resolution, as defined later), (2)

frequency (f), which is inversely related to wavelength, and (3) velocity

of sound (c), which is a constant for any given medium (Fig 1.1A and

B).These three wave characteristics have a set relationship as c = λf An

increase in the frequency (i.e., shortening of the wavelength) implies less

deep penetration due to greater viscous effects leading to more

attenua-tion As the acoustic wave travels through tissue, changes in tissue

prop-erties, such as tissue density, will induce disruption of the propagating

wave, leading to partial reflection (specular reflections) and scatter

(back-scatter) of its energy (Fig 1.2, Box 1.1).4 Typically, specular reflections

originate from interfaces of different types of tissue (such as blood pool

and myocardium or myocardium and pericardium), whereas backscatter

originates from within a tissue, such as myocardial walls In both cases,

reflections propagate backwards to a piezoelectric crystal, again leading

to its deformation, which generates an electric signal The amplitude of

this signal (termed the radiofrequency [RF] signal) is proportional to the

amount of deformation of the crystal (i.e., the amplitude of the reflected

wave) This signal is then amplified electronically, which can be fied by the “gain” settings of the system that will amplify both signal and noise In addition to defining the amplitude of the returning sig-nal, the depth of the reflecting structure can be defined according to the time interval from emitting to receiving a pulse, which equals the time required for the ultrasound to travel from the transducer to the tissue and

modi-back The data on amplitude and depth of reflection are used to form scan

lines, and the overall image construction is based on repetitive operations

of the previously mentioned procedures of image (scan line) acquisition and (post-) processing During image acquisition, transducers emit ultra-

sound waves in pulses of a certain duration (pulse length), at a certain rate, termed the pulse repetition frequency (PRF), which is one of the determi-

nants of the temporal resolution of an echo image (obviously limited by the duration of the pulse-echo measurement [i.e., its determinants]), as elucidated further (see Fig 1.1C)

The data obtained from scan lines can be visually represented as A- or B-mode images (Fig 1.3) The most fundamental modality of imaging

RF signals is A-mode, where A = amplitude, in which such signals are imaged as amplitude spikes at a certain distance from the transducer; how-ever, because visualization of the A-mode signals is relatively unattractive, A-mode is not used as an image display option; further processing is used

to create a B-mode (B = brightness) image in which the amplitudes are displayed by a gray scale (see Fig 1.3) To achieve such gray scale encoding, multiple points of the signal (i.e., pixels) are, based on the local amplitude

of the signal, designated with a number that further represents a color on the gray scale The B-mode dataset can then be displayed as an M-mode (M = motion) image, which displays the imaged structures in one dimen-sion over time (distance of the imaged structures from the transducer is shown on the y-axis, and time is recorded on the x-axis; optimal for assess-ments requiring high temporal resolution and for linear measurements) or

as a 2D image By convention, strong, high-amplitude reflections are given

a bright color and weak, low-amplitude reflections are dark (Box 1.2).Another point in processing the RF signal overcomes a potential tech-nical limitation of echocardiography; namely, reflections from tissues more distant from the transducer are inherently smaller in amplitude, due

to attenuation (see Box 1.1) In practice, this implies that the segments

of the ultrasound image depicting, for example, the atria in the apical

views would be less bright than the myocardium However, attenuation

correction can compensate for this effect, automatically amplifying the

signals from deeper segments, defined as automatic time-gain

compensa-tion (TGC) (Fig 1.4) In addition to the automatic TGC, most systems are equipped with TGC sliders that enable modification of the automated TGC by the operator during image acquisition Because the attenuation effect can be variable among patients, the acquisition of echocardiographic images should commence with a neutral setting of the sliders, which are then individually modified according to the patient and the current echo-cardiographic view Of note, attenuation cannot be corrected for after

Physical Principles of Ultrasound and Generation of Images

Maja Cikes, Jan D’hooge, Scott D Solomon

1

image acquisition The final step in image optimization, which can be

performed during post-processing, is log-compression—most often applied

in diagnostic imaging as the “dynamic range.” This method enables the

increase of image contrast by modifying the number of gray values, thus

leading to nearly black-and-white images (low dynamic range) or more

gray images (high dynamic range).2

Typically, the duration of the pulse-echo event is approximately

200 μs, taking into consideration the usual wave propagation

dis-tance during a cardiac examination (∼30-cm distance from the chest

wall to the roofs of the atria and back) and the speed of ultrasound

propagation through soft tissue This implies that approximately 5000

pulse-echo measurements can be undertaken every second, while

approximately 180 of these measurements are performed in the

con-struction of a typical 2D image of the heart, by emitting pulses in 180

different directions within a 90-degree scanning plane, reconstructing

one scan line for each transmitted pulse In summary, a

construc-tion of one echocardiographic image requires approximately 36 ms

(180 measurements × 200 μs), which translates to approximately 28

frames created per second However, the number of frames (i.e., the

frame rate) can be multiplied by various techniques, some of which are

implemented in most current systems, such as the multiline

acquisi-tion that constructs two or four lines in parallel, leading to a fourfold

increase in the 2D image frame rate.2 For more information on high

frame rate imaging, see Box 1.3

Resolution of Echocardiographic Images

Resolution is defined as the shortest distance between two objects required

to discern them as separate However, resolution in echocardiography, being a dynamic technique, consists of two major components: spatial and temporal resolution Furthermore, spatial resolution mainly comprises axial and lateral resolution, depending on the position of the objects relative to the image line, and various determinants will influence each component of image resolution (Figs 1.5 to 1.7).1–3,5,6 Temporal resolution (i.e., frame rate) represents the time between two subsequent measurements (i.e., the ability of the system to discern temporal events as separate)

Axial resolution refers to resolution along the image line (i.e., two

objects located one behind another, relative to the image line) (see Fig 1.6) Its principal determinant is pulse length (which is, similarly to wavelength, inversely related to frequency), such that a shorter ultra-sound pulse will allow for better axial resolution (typically 1.5 to 2 times the wavelength).2,6 Pulse length is predominantly defined by the characteristics of the transducer: a higher-frequency transducer provides shorter pulses, yielding better axial resolution In practical terms, a typical scanning frequency of 2.5 MHz implies a wavelength

of approximately 0.6 mm, at which an axial resolution of mately 1 mm is obtained However, higher frequencies have reduced penetration due to more attenuation by soft tissue, implying that a compromise between axial resolution and image depth needs to be

ducers can emit pulses of shorter pulse length) These pulses are emitted at a certain rate, termed the pulse repetition frequency (Courtesy of Bernard E Bulwer, MD, FASE.)

Physical Principles of Ultrasound and Generation of Images

3

1

made Therefore high-resolution imaging is predominantly limited to

pediatric echocardiography, where transducers up to 10 to 12 MHz

can be used for infants, as opposed to 2.5- to 3-MHz transducers

typically used in adult echocardiography

Lateral resolution refers to the spatial resolution perpendicular to the

beam (i.e., two objects located next to each other, relative to the image

line) (see Fig 1.7) It is predominantly determined by beam width,

which depends on depth and the size of the transducer footprint (Box

1.4) Lateral resolution will thus be increased with a narrower beam

(i.e., larger transducer footprint and/or shallower scanning depths)

Elevation resolution—resolution perpendicular to the image line—is

somewhat similar to lateral resolution In this case the determinant is the

dimension of the beam in the elevation direction (i.e., orthogonal to the 2D

scan plane) Elevation resolution is more similar to lateral in newer systems

with 2D array transducer technology (compared with 1D transducers)

Temporal resolution, as mentioned previously, is predominantly

determined by PRF, which is limited by the determinants of the tion of the pulse-echo event—the wave propagation distance (the dis-tance from the chest wall to the end of the scanning plane) and the speed of ultrasound propagation through soft tissue (which is consid-ered constant) Frame rate can be increased either by reducing the field

dura-of view (a smaller sector requires the formation dura-of fewer image lines, allowing for a faster acquisition of a single frame) or by reducing the number of lines per frame (line density), controlled by a “frame rate” knob on the system Reduced line density jeopardizes spatial resolu-tion because it sets the image lines further apart There is an intrinsic trade-off between the image field of view, spatial resolution, and tem-poral resolution and should be kept in mind as a potential shortcom-ing of the technique (Box 1.5) For advice on image optimization, see

Box 1.6

FIG 1.2 The interaction of the transmitted wave with an acoustic interface (i.e., cardiac structures) A segment of the transmitted wave is reflected at the interface,

while another part is transmitted through the tissue Such a wave can be refracted, while the transmitted wave may also reflect and return to the transducer (thus carrying information on signal amplitudes) as a specular reflection (mainly occurring at the interfaces of different types of tissue, such as myocardium and pericardium), or as backscatter

reflection (mainly originating from within the myocardial walls) LV, Left ventricle; PM, papillary muscle; PSAX, parasternal short-axis view; RV, right ventricle (Modified from

Bulwer BE, Shernan SK, Thomas J Physics of echocardiography In: Savage RM, Aronson S, Shernan SK, eds Comprehensive textbook of perioperative transesophageal

echocar-diography Philadelphia: Lippincott, Williams & Wilkins; 2009:15.)

Phased Array and Matrix Array Transducers

As opposed to mechanically rotating transducers used in earlier

echo-cardiography systems, contemporary 2D imaging is based on

elec-tronic beam steering This is achieved by an array of piezoelectric

crystals (typically up to 128 elements), while the time delay between

their excitation enables emission of the ultrasound wave in various

directions across the scan plane and the generation of multiple scan

lines (Fig 1.8) The sum of signals received by individual elements

translates to the RF signal for a certain transmission, a process referred

to as beam forming (Box 1.7), which is crucial for acquiring

high-qual-ity images Three-dimensional imaging relies on matrix array

trans-ducers, which are based on a 2D matrix of elements, thus enabling the

steering of the ultrasound beam in three dimensions This allows for

both simultaneous multiplanar 2D imaging, as well as for volumetric

3D imaging.2

Second Harmonic Imaging

Current ultrasound systems are based on fundamental and harmonic

imaging In fundamental imaging the transducer listens for the

ultra-sound of equal frequency to the emitted wave However, at higher

amplitudes of the transmitted wave, wave distortion may occur during

propagation, causing harmonic frequencies (multiples of the

transmit-ted frequency), which can be received by the transducer when properly

implemented (Fig 1.9) Such second harmonic images have significantly

improved signal-to-noise ratio and in particular improved endocardial

border definition However, this comes at the cost of poorer axial

resolu-tion (due to longer transmitted pulses), which may cause some structures,

such as heart valves, to appear thicker on harmonic imaging The

tran-sition between fundamental and harmonic imaging is achieved by the

selection of transmit frequency: lower frequencies automatically enable

harmonic imaging, which is discernible by both the transmit and receive frequency displayed on the screen (e.g., 1.7/3.4 MHz), whereas a single displayed frequency implies fundamental imaging.1,2,5

PRINCIPLES OF DOPPLER IMAGING

Although imaging of the morphology of cardiac structures is increasingly complemented by other modalities such as magnetic resonance imaging (MRI) or computed tomography (CT) imaging, the diagnostic role of echocardiographic imaging in the evaluation of valvular function and noninvasive assessment of hemodynamics remains fairly unique Such

assessments are based on the Doppler principle, which allows for the

FIG 1.3 Generation of images by ultrasound After an ultrasound pulse is emitted

by the piezoelectric crystals located in the transducer (upper left), it travels through

tis-sue, reflects from structures, and propagates backwards to the transducer The received signals undergo processing and are displayed according to their amplitudes and depth

of reflection (upper right) The fundamental A-mode display images the signals as tude spikes (upper right) On B-mode, these amplitude spikes are translated to a gray scale, such that the least reflective tissues (e.g., blood pool) are visualized as black (upper

ampli-right) B-mode images can further be displayed as a two-dimensional cross-sectional

image (bottom left) or in M-mode, which visualizes the imaged structures in one sion over time (bottom right) Note that reflections with the highest amplitudes origi-

dimen-nate from tissue interfaces such as the myocardium and pericardium or blood pool and

myocardium (upper and lower panels) IVS, Interventricular septum; LV, left ventricle;

PW, posterior wall (Courtesy of Bernard E Bulwer, MD, FASE; Modified from Solomon

SD, Wu J, Gillam L, Bulwer B Echocardiography In: Mann DL, Zipes DP, Libby P, Bonow

RO, Braunwald E, eds Braunwald’s heart disease: a textbook of cardiovascular medicine 10th ed Philadelphia: Elsevier; 2015:180.)

sys-tem, where 0 typically represents black, 255 represents white, and the intermediate numbers correspond to hues of gray, which can be extended to a spectrum of, for example, 65,536

reso-lution images Furthermore, contemporary ultrasound systems also offer a choice of color maps, in which case these values cor-respond to hues of, for example, bronze or purple Although gray-scale color maps are most often used, there is no scientific rationale for this and some people prefer to use other color schemes; this thus remains a matter of personal preference

BOX 1.2 Color Maps

The attenuation of soft tissue is typically expressed in decibel

per cm per MHz (i.e., dB/cm per megahertz), given that the

attenuation is dependent on both frequency and propagation

distance of the wave A typical value for attenuation in soft

tis-sues is 0.5 dB/cm per megahertz, implying that for 20-cm

propa-gation (e.g., from the probe to the mitral annulus and back

for an apical transducer position) of a wave generated by a

common adult cardiac ultrasound transducer (i.e., 2.5 MHz) the

amplitude of the acoustic wave has decreased by 25 dB,

mean-ing that the wave received back at the probe surface will—at

best (i.e., assuming perfect reflection and optimal focusing)—

have only 5% of the amplitude of the transmitted wave When

doubling the frequency to 5 MHz (i.e., pediatric probe) the

total attenuation doubles to 50 dB, implying that only

approxi-mately 0.3% of the transmitted amplitude returns from 20 cm

deep, which can become difficult to detect Hence the proper

choice of transducer is required based on the depth at which

structures need to be visualized

Reflection and refraction of sound waves occur at

struc-tures of differing acoustic impedance (i.e., mass density and/or

compressibility) that are large compared with the wavelength

(i.e., significantly > 0.5 mm for a 2.5 MHz wave) In this case the

behavior of acoustic waves is very similar to optic (i.e., light)

waves: part of the energy is transmitted into the second medium

under a slightly different angle (i.e., the refracted wave) while

part of the energy is reflected (i.e., the reflected wave) As a

simple example, you can think of what you see when holding

your hand under water: your arm appears to make an angle

at the water surface The reason is light wave refraction at the

water surface, and the exact same phenomenon exists for

ultra-sound waves One may thus think that the posterior wall would

appear distorted (cf your arm under water) due to the wave

being refracted at the septal wall interfaces Although this is

true, in practice these refraction effects are—luckily—most often

negligible

BOX 1.1 Attenuation, Reflection, and Refraction of

Ultrasound Waves

Physical Principles of Ultrasound and Generation of Images

5

1

calculations of blood velocities within the heart or in blood vessels.1–3,5,6

The Doppler effect states that the frequencies of transmitted and received

waves differ when the acoustic source moves towards or away from the

observer (due to wave compression or expansion, depending on the

direction of motion) (Fig 1.10) For example, this is noticed as a

higher-pitched sound of the siren as the ambulance approaches the observer,

compared with it moving away The Doppler effect can be applied to measuring blood (and tissue) velocities, by measuring the difference between the frequency of emitted and received ultrasound, which will be reflected off moving red blood cells Should the blood cells be moving in the direction of the transducer, the reflected waves will be compressed and the frequency of the received ultrasound will be higher compared with the emitted ultrasound Conversely, the frequency of the received ultrasound will be lower with blood cells moving away from the transducer This dif-

ference between the emitted and received frequency is termed the Doppler

shift or Doppler frequency, which is directly proportional to the velocity of

the reflecting structures (red blood cells, i.e., blood flow):

fd= 2 ftv (cos θ) /c

where fd is the Doppler frequency, ft is the original transmitted ultrasound

frequency, v is the magnitude of the velocity of blood flow, θ stands for

the angle between the ultrasound beam and the blood flow (i.e., the angle

of incidence/the angle of insonation), and c is the velocity of ultrasound

through soft tissue (1530 m/s) The main limitation of the Doppler equation is the angle of incidence, such that its increase decreases the calculated velocity: cos 0 degrees = 1, which implies that data acquisition with the ultrasound beam parallel to the direction of blood flow would be ideal; conversely, cos 90 degrees = 0, implying that motion orthogonal to the ultrasound beam cannot be detected regardless of the velocity magni-tude Practically, an angle lower than 20 degrees is considered adequate for acceptable measurements (of note, there is no possibility of velocity over-estimation due to this phenomenon) To optimize alignment, Doppler imaging can be used in conjunction with 2D imaging, which allows for optimal placement of the Doppler cursor prior to Doppler data acquisi-tion Furthermore, should the angle of incidence be known, it can be corrected for in the Doppler equation of the velocity estimate by means of

a feature available on many ultrasound systems, usually termed angle

cor-rection However, this is acceptable for laminar flow conditions (typically

in vascular ultrasound, in particular of nonstenosed vessels), whereas the exact direction of flow within the heart is, in fact, unknown For this rea-son, it is not recommended to use angle correction in cardiac ultrasound (or if applied, use with caution and awareness of the issue)

FIG 1.4 Attenuation correction settings Optimal settings of time-gain compensation (TGC) can provide a uniform display of signal intensity for echoes from similarly

reflecting structures, across various depths of the scan sector (From Bulwer BE, Shernan SK Optimizing two-dimensional echocardiographic imaging In: Savage RM, Aronson S,

Shernan SK, eds Comprehensive textbook of perioperative transesophageal echocardiography Philadelphia: Lippincott, Williams & Wilkins; 2009:59.)

Multiple approaches have been proposed to increase frame

rate (i.e., time resolution) of the echocardiographic

record-ings Most high-end commercially available systems reconstruct

2 to 4 image lines from each transmitted pulse, but 3D

imag-ing systems reconstructimag-ing up to 64 lines for each transmit are

commercially available Although this “parallel beam forming”

results in better time resolution of the images, it typically comes

at the cost of reduced spatial resolution and/or signal-to-noise

ratio of the images Finding the optimal compromise between

these parameters is a major challenge for all vendors of

ultra-sound equipment Alternative imaging techniques to speed

up the acquisition process but with potentially less effects

on spatial resolution and signal-to-noise ratio (e.g., multiline

transmit and diverging wave imaging) are being developed

Two popular approaches that are currently being explored are

“multiline transmit” imaging and “diverging wave” imaging

For the former a number of pulse-echo measurements are done

in multiple directions in parallel, a challenge being to avoid

crosstalk between the simultaneously transmitted pulses In

the latter technique the whole field of view (or a large part

of it) is insonified by a very wide (i.e., defocused) ultrasound

beam, allowing to reconstruct the whole image with a very

small number of transmits (i.e., 1 to 5) In this way, frame rate is

increased tremendously (up to 1 to 5 kHz), the challenge being

to preserve spatial resolution and contrast of the images (i.e.,

image quality) Despite these remaining challenges, fast

imag-ing approaches will undoubtedly enter clinical diagnostics in

the years to come

BOX 1.3 High Frame Rate Imaging

Continuous Wave Doppler

The Doppler modalities used in echocardiography are pulsed wave (PW)

and continuous wave (CW) Doppler (Fig 1.11), as well as color flow

mapping (color flow Doppler) In CW, separate piezoelectric crystals

continuously emit and receive ultrasound waves, and the difference

between the frequencies of these waves (the Doppler shift) is calculated

continuously In PW Doppler, ultrasound is emitted in pulses, as is the

case with standard image acquisition According to the Doppler equation,

the Doppler shift is translated to velocity, which is then displayed over

a certain time frame (determined by the sweep speed of the image), and

is termed the spectrogram As red blood cells travel at different velocities

within the ultrasound beam, various receive frequencies will be detected,

implying that a spectrum of Doppler shifts will be calculated and

dis-played on the spectrogram—thus termed spectral Doppler (Fig 1.12)

In CW the spectrum is rather broad due to the large sample volume,

which accounts for a wide range of detected velocities, as opposed to

PW Although ultrasound is well beyond the limits of human hearing,

the frequencies of the Doppler shift for typical blood velocities are

actu-ally within the audible range and can be heard during an examination:

a higher-pitched sound corresponds to higher velocities (larger Doppler

shift), whereas lower velocities generate a lower-pitched sound (smaller

Doppler shift) Furthermore, because the ultrasound waves are emitted

(and received) continuously in CW (i.e., the ultrasound system is not

“waiting” for the reflection and return of the emitted pulse), the

loca-tion of the reflected sound cannot be determined and therefore no

spa-tial information is available by CW However, all frequency shifts (i.e.,

velocities) along the beam are measured, which allows for high-velocity

measurements by CW, typically used in the assessment of high velocities

(turbulence) across the aortic valve in patients with aortic stenosis or in

the approximation of pulmonary artery pressure from the velocity of the

tricuspid regurgitation jet As is the case in 2D imaging the attenuation

effect also takes place in CW, as a consequence of which velocities from

deeper tissue contribute less to the displayed signal (Fig 1.13) For advice

on CW Doppler optimization, see Box 1.8

Pulsed Wave Doppler

As opposed to CW, in PW Doppler ultrasound is emitted and received

in a similar manner to 2D imaging: individual pulses are emitted as brief, intermittent bursts After emitting such a pulse, the transducer “listens” to returning signals only during a short, defined time interval following pulse emission This time interval corresponds to the time required for the pulse to reach a certain depth and travel back to the transducer The depth is defined

by the sample volume—in practical terms, a cursor that the operator places at

a certain depth along the transmitted beam, on the superimposed 2D image; technically, this implies adjusting the timing between signal emission and reception.7 Furthermore, the previously mentioned pulse-echo measure-ment is repeated along a specific line, at a specific repetition rate, termed the

PRF (i.e., the number of pulses transmitted from transducer per second)

Such pulses require time to reflect and travel back to the transducer; thus the interval at which they are transmitted has to be long enough for the ultra-sound system to be able to discern whether the reflected signal originates from the given pulse or a later one Based on this concept the velocity of blood can be measured at a specific location in the heart by PW, thereby providing spatial information on flows Therefore PRF represents the sam-pling rate of the ultrasound machine: higher blood velocities imply higher Doppler shift frequencies, requiring a higher sampling rate to detect the shift (Box 1.9) Notably, PRF should not be mistaken for the frequency of the ultrasound wave: in analogy to music, the PRF denotes the rate at which a certain note is repeated, whereas the ultrasound wave frequency corresponds

to the pitch of a certain note.5 The PRF is a principal determinant of the maximal Doppler shift (i.e., the maximal velocity within the sample volume that the ultrasound system can accurately quantify) This maximal velocity

is also referred to as the Nyquist frequency (or the Nyquist limit) and is the

maximal velocity that can be accurately interrogated within a certain sample volume It is directly related to PRF, which is inversely related to the distance between the transducer and sample volume The Nyquist limit equals one-half of the PRF When imaging flows with velocities higher than double the PRF value, sampling of the waveform is inaccurate, disabling the accurate

assessment of velocities, which can be detected by the appearance of aliasing

FIG 1.5 Components of spatial resolution Lateral resolution refers to the spatial resolution perpendicular to the beam, axial resolution refers to resolution along the

image line, and elevation resolution is also perpendicular to the image line; however, its determinant is the dimension of the beam in the elevation direction (Modified from

Bulwer BE, Shernan SK Optimizing two-dimensional echocardiographic imaging In: Savage RM, Aronson S, Shernan SK, eds Comprehensive textbook of perioperative

trans-esophageal echocardiography Philadelphia: Lippincott, Williams & Wilkins; 2009:54.)

Physical Principles of Ultrasound and Generation of Images

7

1

FIG 1.6 Features of axial resolution are based on pulse duration (spatial pulse, length), which is predominantly defined by the characteristics of the transducer (i.e., its frequency) (A) The two reflectors (echo 1 and echo 2) are located apart enough to be resolved by the separately returning echo pulses (B) The two reflectors (echo 1

and echo 2) are located too close, and the returning echo pulses will merge (C) An increase in the transducer frequency from 3 to 7 MHz will shorten the spatial pulse length

(and pulse duration), thus permitting the returning echoes from these reflectors to be resolved (Courtesy of Bernard E Bulwer, MD, FASE.)

in the generated image Aliasing occurs due to the inability of the system to

accurately determine the velocity or direction of flow at velocities

exceed-ing the Nyquist limit (Fig 1.14) To avoid aliasing, a higher PRF should be

used, although a lower PRF will enable a better estimation of the blood flow

velocity—thus the lowest PRF possible without introducing aliasing should

be used Depending on the machine, the PRF adjustment is referred to as

“scale,” “velocity range,” or “Nyquist velocity.”1–3,5,6 In addition, the baseline

of the spectrogram should be shifted upwards in case of flow away from the

transducer and downwards in case of flow towards the transducer, allowing for higher velocities to be measured Finally, a lower or higher PRF needs to

be applied depending on the depth of the measured flow: to “reach” flows at greater depths (further from the transducer) and carry the information back

to the receiver, a lower PRF needs to be used, compared with flows closer to the transducer In practice, this is particularly obvious when measuring pul-monary vein flow in the apical views: a dedicated “low PRF” button on the ultrasound system can be helpful to obtain an instantaneous shift in PRF and improve signal quality In analogy, higher velocities can be sampled without aliasing at sample volume positions closer to the transducer For advice on

PW Doppler optimization, see Box 1.10 and Fig 1.15

Color Flow Doppler

Color Doppler processing is based on PW Doppler imaging ogy; however, in color flow Doppler the time shift between subsequent measurements is determined at multiple sample volumes along multiple scan lines The calculated velocities are linked to a preset color scheme

technol-by means of a specific color map (displayed on the ultrasound image,

Fig 1.16), according to which the direction of flow and its velocity amplitudes can be determined By convention, flow away from the trans-ducer is colored in blue, whereas flow towards the transducer is coded

in red The color flow Doppler data are displayed superimposed on a 2D or M-mode image, allowing for visualization of flow patterns with

FIG 1.7 Lateral resolution is predominantly determined by beam width, such that a narrower beam will allow for greater lateral resolution.

As a first approximation the beam width can be calculated as:

“D” the dimension of the transducer footprint The ratio of d/D

is called the f-number of the transducer From the previous

equa-tion, it is clear that transducer size directly impacts the spatial

resolution for a given depth Unfortunately, for cardiac

applica-tions, transducer footprint needs to remain limited (and hence

the spatial resolution) due to the limited size of the acoustic

win-dow towards the heart (i.e., the intercostal space) Although, for

example, fetal cardiac imaging is possible with a cardiac

ultra-sound probe, image resolution will intrinsically be much better

when using a large, curved array as used in obstetrics

BOX 1.4 Beam Width

The trade-off between spatial resolution, temporal resolution,

signal-to-noise ratio and field of view of the echocardiographic

data is intrinsic and application dependent Indeed, when

mea-suring, for example, the dimensions of a given cardiac

struc-ture, time resolution may be less critical and system settings

could be adjusted to get the best possible spatial resolution

and signal-to-noise ratio at the cost of time resolution On the

other hand, when making a functional analysis of the heart

(e.g., when applying speckle tracking), improved time

resolu-tion may be important and justify reducing the overall image

quality It is thus important to realize that optimal acquisition

settings are application dependent

BOX 1.5 The Trade-off Between Temporal and Spatial

• Optimize depth and focus according to imaged structure; use minimal depth settings

• Optimize gain and dynamic range settings to obtain mal image contrast: start with a black blood pool, increas-ing gain to a minimal amount that allows for definition of the heart structures

• Time gain compensation should be used to homogenize the image at various depths; start at a neutral position of the sliders

BOX 1.6 Image Optimization General Points

Physical Principles of Ultrasound and Generation of Images

9

1

additional information on the spatial location of the flow, nature of the

flow (turbulence, direction of flow), geometry of potential connections

between the heart chambers or great vessels, etc Due to the same basic

principles of PW Doppler, color flow Doppler is also subject to

alias-ing, whereas a high variance of velocity in a particular pixel is mostly

displayed as shades of green, which is indicative of turbulent flow Similar

to PW Doppler, the appearance of aliasing can be reduced by increasing

the PRF (however, PRF is coupled to velocity resolution) or by reducing

the transmission frequency (rarely performed) The generation of a color

flow Doppler image requires more “computing” time, and, to retain an acceptable temporal resolution, it is suggested that the region of color flow imaging (i.e., the color box) is kept to the minimal size required.1,2,5

For advice on color flow Doppler optimization, see Box 1.11

Doppler Echocardiography in the Assessment of Hemodynamics

Doppler echocardiography is predominantly used for the assessment of velocities of blood flow within the heart and great vessels, which are deter-mined by the driving pressure gradients between these structures (i.e., across heart valves) Analogously, the measured velocities of blood flow across a certain valve can be used in the assessment of pressure gradi-ents between the relevant chambers: based on conservation of energy, the

Bernoulli equation defines the relation between pressures and velocities for

fluids in chambers separated by an orifice:

P1− P2= 1

2ρ V2− V2 + ρ∫12dv dt ds + R v

Connective Acceleration Flow Acceleration Viscous Friction

where P1 and P2 represent the pressures, and V1 and V2 represent the velocities proximal and distal to the orifice.1

In daily practice a simplified form of the Bernoulli equation may be used, not taking into account flow acceleration and viscous friction:

P1− P2= 1/2ρ V2− V2Velocities proximal to the stenosis (i.e., orifice) are usually rather low (when comparing with those distal to the stenosis) and may thus generally

be ignored, which further simplifies the equation:

P1− P2= 4V2Some of the most frequent applications of the Bernoulli equation in the assessment of hemodynamics include the evaluation of the peak sys-tolic gradient across the aortic valve in aortic stenosis: Doppler echocar-diography can assess the peak velocity of antegrade blood flow across the stenosed aortic valve, whereas applying the modified Bernoulli equation

FIG 1.8 The phased array transducer technology Current echocardiography transducers steer the ultrasound beam (also termed sweep) across the scan plane, thus

creat-ing a fairly wide scan sector (center) Durcreat-ing ultrasound transmission the time delays in activatcreat-ing the piezoelectric crystals induce the sweep of the scan line over the scan plane

(left) During reception, the reflected echo signals are out of phase when received by each crystal and need to be shifted in time (i.e., phased) prior to summation and further

processing (right) (Courtesy of Bernard E Bulwer, MD, FASE; Modified from Solomon SD, Wu J, Gillam L, Bulwer B Echocardiography In: Mann DL, Zipes DP, Libby P, Bonow RO,

Braunwald E, eds Braunwald’s heart disease: a textbook of cardiovascular medicine 10th ed Philadelphia: Elsevier; 2015:180.)

Phased array transducers enable steering and focusing of the

ultrasound beam simply by adjusting the electrical excitations

Similarly, during reception, the received signals coming from

individual transducer elements will be delayed in time to

cor-rect for the differing time of flight of a given echo to the

indi-vidual transducer elements as a result of the differences in path

former is referred to as “transmit focusing,” whereas the

lat-ter is “receive focusing.” Inlat-terestingly, during receive focusing,

one can dynamically adjust the focus point as one knows a

pri-ori from which depth echo signals are arriving at a given time

point after transmission given the sound velocity is known As

such, the time delays applied to the signals coming from the

different elements is adjusted dynamically in time to optimally

focus the ultrasound beam at all depths Similarly, given that

ele-ments near the edge of the probe can be switched off when

(receive) focusing close to the probe to reduce the effective

transducer size, thereby making its ability to focus worse The

advantage of this approach is that the beam width becomes

more uniform as a function of depth and thus so does the

lateral image resolution These beam-forming modalities are

referred to as “dynamic receive focusing” and “dynamic

apo-dization,” respectively, and are implemented on all cardiac

ultrasound systems

BOX 1.7 Beam Forming

FIG 1.9 Tissue harmonic imaging Tissue harmonic imaging allows for improved image quality by using second-order harmonics in which specific frequencies of ultrasound

induce tissue vibrations at twice the frequency Listening for such higher frequencies of returning ultrasound allows for dramatic improvement of the signal-to-noise ratio

Second-harmonic imaging provides images with clearly ameliorated tissue definition and less affected by acoustic noise and artifacts (right) (Courtesy of Bernard E Bulwer, MD,

FASE; From Solomon SD, Wu J, Gillam L, Bulwer B Echocardiography In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds Braunwald’s heart disease: a textbook of

cardiovascular medicine 10th ed Philadelphia: Elsevier; 2015:181.)

FIG 1.10 The Doppler principle and Doppler frequency shift Ultrasound emitted from the transducer reflects off moving red blood cells and returns to the transducer:

if reflected from red blood cells moving in the direction of the transducer, the echo returns at a higher frequency (shorter wavelength) than the emitted ultrasound pulse (upper

left); conversely, if blood cells are moving away from the transducer, a lower-frequency echo will be reflected back to the transducer (lower left) The difference between the

transmitted and the returning frequency equals the Doppler shift, which is used by Doppler echocardiography systems to calculate velocities of blood flow These velocities are graphically displayed by spectral Doppler as a time velocity spectrum (spectrogram), where a positive Doppler shift (implying flow toward the transducer) is depicted above the

baseline, and a negative Doppler shift (flow away from the transducer) is drawn below the baseline (right) In color flow Doppler the direction of flow can be detected according

to the color-coded velocities (Courtesy of Bernard E Bulwer, MD, FASE; Modified from Solomon SD, Wu J, Gillam L, Bulwer B: Echocardiography In Mann DL, Zipes DP, Libby P,

Bonow RO, Braunwald E, eds Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine 10th ed Philadelphia: Elsevier; 2015:182.)

Physical Principles of Ultrasound and Generation of Images

11

1

FIG 1.11 Comparison of continuous wave (CW) Doppler and pulsed wave (PW) Doppler (Courtesy of Bernard E Bulwer, MD, FASE; Modified from Solomon SD, Wu

J, Gillam L, Bulwer B Echocardiography In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds Braunwald’s heart disease: a textbook of cardiovascular medicine 10th

ed Philadelphia: Elsevier; 2015:182.)

FIG 1.12 The properties of spectral Doppler The velocity of blood flow is

graphically displayed on the y-axis, and time is on the x-axis Flow direction can also

be determined, depending on the relation of the spectrogram to the baseline: flow

toward the transducer is imaged above and flow away from the transducer is imaged

below the baseline The signal intensity reflects the quantity of red blood cells that are

moving at a specific velocity range In continuous wave the spectrum is rather broad

due to the wide range of velocities detected by the beam, as opposed to pulsed wave

(which is imaged here) A4C, Apical four-chamber.

FIG 1.13 The depth attenuation effect seen on continuous wave (CW) Doppler in aortic stenosis With minimal gain settings, it can be appreciated that

the velocities from deeper tissues contribute less to the spectrogram: the Doppler signal from the aortic root is attenuated and much weaker than that from the left ventricular outflow tract (LVOT) With higher Doppler gain (second heart cycle), the

effect is less obvious A5C, Apical five-chamber.

allows for the estimation of the peak instantaneous transvalvular gradient,

relevant for the assessment of aortic stenosis severity Another frequently

used example refers to the assessment of peak systolic right ventricular

and pulmonary artery pressure: it is derived by adding the peak velocity

of the tricuspid regurgitation jet, which indicates the pressure gradient

between the right ventricle and right atrium in systole, to the right atrial

pressure estimate (which can also be determined by echocardiography,

according to the diameter and respiratory collapse of the inferior vena

cava) However, the Bernoulli equation can be used in all cases in which

a velocity gradient is present: valvular stenosis or regurgitation, as well

as abnormal connections (ventricular septal defect, etc.) Importantly, it

should be kept in mind that Doppler echocardiography enables the

mea-surement of velocity, from which pressures and flows are inferred—the

absolute pressures in cardiac chambers can only be measured invasively.1

Another physical principle that is frequently used in the assessment

of hemodynamics is the continuity of flow equation, which states that the

same volume/flow passes through different cross sections of a tube (i.e.,

the heart), assuming no loss of fluid (i.e., no shunt) This equation is

typi-cally applied in the assessment of volumes/flows and valve areas: by

mul-tiplying the cross-sectional area (CSA) of the interrogated orifice by the

time velocity integral (TVI, i.e., the integration of blood velocity across

an orifice during one cardiac cycle) at the corresponding level, the

magni-tude of flow can be assessed (Fig 1.17)

Furthermore, because a CSA of a diseased valve may be difficult to

measure, valve area can be calculated by estimating the flow proximal to

the valve and the TVI at the level of the valve A frequently used example

includes the assessment of aortic valve CSA in aortic stenosis: according

to the continuity equation, the flow through the left ventricular outflow

tract (LVOT) equals that through the aortic valve, that is:

TVILVOT× AreaLVOT= TVIAV× AreaAV→ AreaLVOT=

(TVIAV× AreaAV)/ TVILVOT

Obviously, such a calculation is prone to pitfalls that are mainly due to erroneous measurement of the LVOT diameter, suboptimal positioning of the PW Doppler sample volume in the LVOT, or malacquisition of the peak velocities by CW Doppler across the aortic valve

An overview of hemodynamic data that can be derived from Doppler echocardiography is given in Fig 1.18 More detailed explanations of specific measurements and entities will be given in further chapters of the book

• Optimize beam alignment with the direction of measured

velocity (direction of flow)

• Optimize gain to create a uniform Doppler profile free

of “blooming”: to prevent loss of data due to insufficient

gain, start with an overemphasized image, decreasing the

gain to a minimal required amount

• Optimize the “compress” control (assigns a certain shade

of color to varying amplitudes): extreme values can affect

the quality of the spectral analysis

• The “low velocities reject” button discards the signals of

lower amplitude, providing a cleaner image and more

precise measurements

• The “filter” reduces noise occurring from reflectors

origi-nating from the myocardium and other heart structures

BOX 1.8 Continuous Wave Doppler Optimization

Points

High PRF PW Doppler is also optional on some systems and can

be recognized by the occurrence of several sample volumes

along the Doppler beam The measurement concept is based

on the fact that the PW Doppler system knows exactly when

to sample the echo signal (i.e., at the sample volume) As such,

a new pulse can already be transmitted (to a more proximal/

distal sample volume) before the echoes of the original

trans-mit have been received without inducing artifacts Thus the PRF

(and Nyquist limit) can be increased by emitting one (or more)

new pulses prior to receiving the signal of the first pulse from

the expected depth However, such construction of the

spectro-gram implies that the exact location of the origin of the signal

along the Doppler beam cannot be known

BOX 1.9 High Pulse Repetition Frequency Pulsed Wave

Doppler

FIG 1.14 The explanation of aliasing based the “wagon wheel” example, stemming from the wagon wheel illusion seen in old western motion pictures (an

example from sampling theory): envision a rotating clock hand—in the top panel, it

rotates at one revolution per minute If one would “sample” the clock 4 times per minute (every 15 seconds) by shooting a picture, one could easily “capture” the motion of the clock, could comprehend that the direction of rotation is clockwise, and could perceive the rate of rotation However, if the rotational speed were to be increased to two revolutions per minute, maintaining the sampling rate, one would

“capture” only the hand at 12 o’clock and 6 o’clock, still being able to discern the

rate of rotation, but not the direction (middle panel) Ultimately, if the revolution

velocity increased to three revolutions per minute (in the same direction), ing the same sampling rate, the perceived rate of rotation would be one revolu-

retain-tion per minute while the perceived direcretain-tion would be counterclockwise (bottom

panel) In analogy to pulsed wave Doppler, at a certain sampling rate of the

sys-tem, increasing velocities of blood flow cannot be assessed adequately, neither for

their velocity, nor direction of blood flow (From Solomon SD Echocardiographic

instrumentation and principles of Doppler echocardiography In: Solomon SD, ed

Essential echocardiography—a practical handbook with DVD Totowa, NJ, Humana

• Shift the baseline upwards or downwards to use the entire display for either forward or backward flow (useful in unidirectional flows)

• Optimize the PRF: use as high as possible to detect high velocities, avoiding aliasing

• Use low PRF for flows distant from the transducer

• Use high PRF with caution if the origin of flow is relevant

BOX 1.10 Pulsed Wave Doppler Optimization Points

CW, Continuous wave, PRF, pulse repetition frequency.

Physical Principles of Ultrasound and Generation of Images

13

1

FIG 1.15 The effect of sample volume position on the mitral inflow pattern For the assessment of left ventricular diastolic function, the pulsed wave Doppler sample

volume should be positioned at the tips of the mitral valve leaflets, which would correspond to the mitral inflow pattern shown under the letter “E.” As can be observed, even

small deviations from this position can dramatically impact the pattern as well as the obtained measurements, thus rendering an inaccurate assessment of diastolic function LA, Left atrium; LV, left ventricle; MV, mitral valve; RA, right atrium; RV, right ventricle (Modified from Appleton CP, Jensen JL, Hatle LK, Oh JK Doppler evaluation of left and right

ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings J Am Soc Echocardiogr 1997;10(3):271-292, with permission.)

FIG 1.16 Color flow Doppler imaging Color flow Doppler is superimposed on the two-dimensional image By convention, blood flow with mean velocities traveling

toward the transducer is encoded in red, and mean velocities moving away from the transducer are color-coded in blue Similar to other forms of PW Doppler, high velocities and turbulent flow are subject to aliasing, which is in color flow Doppler depicted as a multicolored mosaic pattern (typically green and yellow) The color-velocity scale illustrates incre-

mental velocities in both directions from the baseline, such that higher velocities appear in increasingly lighter hues A4C, Apical four-chamber; BA RT, blue away - red toward; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle (Courtesy of Bernard E Bulwer, MD, FASE; Modified from Solomon SD, Wu J, Gillam L, Bulwer B Echocardiog-

raphy In: Mann DL, Zipes DP, Libby P, Bonow RO, Braunwald E, eds Braunwald’s heart disease: a textbook of cardiovascular medicine 10th ed Philadelphia: Elsevier; 2015:183.)

Doppler Tissue Imaging

The principles of Doppler imaging are also applied to Doppler tissue

imaging (DTI)—a modality in which the measured velocities are those

of myocardial motion, rather than blood flow This is obtained by the

use of contrasting filters: when imaging blood flow, low velocities of

strongly reflecting structures (such as the myocardium) should be filtered

out; conversely, the filters omit high velocities of low scattering structures

(such as red blood cells) while performing DTI.8,9

The basic quantification performed by DTI is that of velocities

of myocardial motion (with regard to the transducer) at all points

within the cardiac cycle, at any segment of the myocardium, thus also providing insight to regional myocardial function The typical DTI waveforms reveal systolic contraction (S′), early diastolic relaxation (E′), and late diastolic relaxation velocities (A′) DTI data can be obtained by both pulsed wave (spectral) Doppler and color Doppler Accordingly, the inherent limitations of Doppler imaging, such as angle dependence, apply to DTI as well, reinforcing the necessity of optimal beam alignment with the direction of myocardial motion Furthermore, it should be noted that the absolute recorded velocities are not equal for the PW and color DTI technique: PW DTI veloci-ties represent peak velocities and are thus higher than those obtained

by color DTI.8,9

One of the principal advantages of DTI is its high temporal tion (usually between 150 and 200 Hz), which is typically obtained by imaging myocardial walls within narrow sectors Conversely, one of the shortcomings of DTI-based velocity measurements is their dependency

resolu-on the overall motiresolu-on of the heart Thus additiresolu-onal modalities have been developed to better assess the deformation (as opposed to motion)

of specific myocardial segments In the DTI approach the calculation

of spatial gradients of the obtained velocities of neighboring myocardial segments allows for the quantification of local myocardial deformation (i.e., strain-rate) However, strain-rate curves may be rather “noisy,” and a temporal integration of such curves is often performed to extract strain values In more practical terms, strain-rate represents the speed

of myocardial deformation (s-1) and can be expressed for both systolic

FIG 1.17 Stroke volume calculation from Doppler measurements, which can be applied on all four heart valves A5C, Apical five-chamber view; CSA, cross-sectional area;

HR, heart rate; LA, left atrium; LV, left ventricle; LVOT, left ventricular outflow tract; PLAX, parasternal long-axis view; PW, pulsed wave Doppler; SV, stroke volume; VTI, velocity

time integral.

• Optimize the size of the color box to the smallest necessary

size

• Optimize gain settings: start with overemphasized gain

such that background noise is detectable, reduce until

disappearance of background noise

• Optimize the Nyquist scale according to the measured

velocities: with high velocities, chose a high Nyquist limit

(e.g., mitral regurgitation), and a low Nyquist limit when

measuring low velocities (e.g., pulmonary vein flow)

BOX 1.11 Color Flow Doppler Optimization Points

Physical Principles of Ultrasound and Generation of Images

15

1

and diastolic events, whereas strain corresponds to the amount of deformation (%), typically referring to systolic deformation The men-tioned quantification can be performed for all three major components

of myocardial deformation: longitudinal, radial, and circumferential deformation (Fig 1.19).8,9

2D Speckle Tracking Echocardiography

For information on this topic, refer to Chapter 6

Suggested Readings

Armstrong, W F., & Ryan, T (Eds.) (2010) Feigenbaum’s Echocardiography (7th ed.) Philadelphia: Lippincott

Williams & Wilkins.

Bijnens, B H., Cikes, M., Claus, P., & Sutherland, G R (2009) Velocity and deformation imaging for the

assessment of myocardial dysfunction European Journal of Echocardiography, 10, 216–226.

D’hooge, J., & Mertens, L L (2016) Ultrasound physics In W W Lai, L L Mertens, M S Cohen, & T

Geva (Eds.), Echocardiography in Pediatric and Congenital Heart Disease: From Fetus to Adult (2nd ed.)

(pp 2–18) Chichester: John Wiley and Sons.

Solomon, S D (Ed.) (2007) Essential Echocardiography—A Practical Handbook with DVD Totowa, New

Jersey: Humana Press.

Szabo, T L (Ed.) (2014) Diagnostic Ultrasound Imaging: Inside Out (2nd ed.) Amsterdam: Elsevier.

A complete reference list can be found online at ExpertConsult.com

FIG 1.18 Hemodynamic data obtainable by Doppler echocardiography.

circumferential

shortening

rotation

Apical

radialmotion

radialmotionlongitudinal

motion

(longitudinal) shortening

(radial)thickening

FIG 1.19 Three major components of myocardial motion and deformation: longitudinal, radial, and circumferential (A and B) The total deformation of a myocardial segment from end-diastole to end-systole includes shortening, thickening, and shearing (B) Typical waveforms of myocardial velocity and displacement (C), as well as strain-rate, strain (D)

over a cardiac cycle of a normal individual AVC, Aortic valve closure; MVO, mitral valve opening (From Bijnens BH, Cikes M, Claus P, Sutherland GR: Velocity and deformation

imaging for the assessment of myocardial dysfunction Eur J Echocardiogr 2009;10(2):216-226 Reprinted with permission.)

1

References

1 Solomon, S D., Wu, J., Gillam, L., & Bulwer, B (2015) Echocardiography In D L Mann, D P Zipes,

P Libby, R O Bonow, & E Braunwald (Eds.), Braunwald’s Heart Disease: A Textbook of Cardiovascular

Medicine (10th ed.) (pp 179–260) Philadelphia: Elsevier.

2 D’hooge, J., & Mertens, L L (2016) Ultrasound physics In W W Lai, L L Mertens, M S Cohen, & T

Geva (Eds.), Echocardiography in Pediatric and Congenital Heart Disease: From Fetus to Adult (2nd ed.) (pp

2–18) Chichester: John Wiley and Sons.

3 Armstrong, W F., & Ryan, T (Eds.) (2010) Feigenbaum’s Echocardiography (7th ed.) Philadelphia:

Lippincott Williams & Wilkins.

4 Savage, R M., Aronson, S., & Shernan, S K (Eds.) (2010) Comprehensive Textbook of Perioperative

Transesophageal Echocardiography Philadelphia: Wolters Kluwer.

5 Solomon, S D (Ed.) (2007) Essential Echocardiography—A Practical Handbook with DVD Totowa, NJ:

Humana Press.

6 Weyman, A E (Ed.) (1994) Principles and Practice of Echocardiography (2nd ed.) Philadelphia: Lippincott

Williams & Wilkins.

7 Appleton, C P., Jensen, J L., Hatle, L K., & Oh, J K (1997) Doppler evaluation of left and right

ven-tricular diastolic function: a technical guide for obtaining optimal flow velocity recordings Journal of the American Society of Echocardiography, 10, 271–292.

8 D’hooge, J., & Rademakers, F (2008) Myocardial motion/deformation—principles In G R Sutherland,

L Hatle, P Claus, J D’hooge, & B H Bijnens (Eds.), Doppler Myocardial Imaging—A Textbook (pp

5–18), Hasselt: BSWK.

9 Bijnens, B H., Cikes, M., Claus, P., & Sutherland, G R (2009) Velocity and deformation imaging for the

assessment of myocardial dysfunction European Journal of Echocardiography, 10, 216–226.

INTRODUCTION

M-mode echocardiography provides superior temporal resolution, and

therefore subtle changes are more readily appreciated with m-mode than

with two-dimensional or three-dimensional methods M-mode methods

may include more precise measurement of cardiac chambers (provided

they are obtained on-axis), independent motion of valvular vegetations,

early closure or early opening of valve structures with respect to timing

in the cardiac cycle (Fig 2.1), identification of prosthetic valves and their

function, assessment of paradoxical interventricular septal motion and

dyssynchrony of the left ventricle, as well as fluttering of valve leaflets

seen in association with valvular regurgitation (Fig 2.2) The exaggerated

motion, as well as restricted motion, of various cardiac structures is

read-ily appreciated with m-mode

An m-mode echocardiogram provides one-dimensional information

regarding a particular cardiac structure as it relates to time and distance,

with time displayed on the horizontal axis and depth or distance

dis-played on the vertical axis The strength of the reflected echo is

repre-sented as the brightness of structures appearing on the image display

(Fig 2.3) The limitations of m-mode echocardiography relate to having

to draw conclusions in one dimension about a three-dimensional

struc-ture Furthermore, measurements are dependent on the identification of

clearly defined borders, which may not be obtainable in technically

chal-lenging patients With respect to m-mode’s derived ejection fractions,

calculations may not be accurate when regional wall motion

abnormali-ties are present

Although m-mode echocardiography was described more than 50

years ago by Edler and Hertz, new concepts and technologies that take

advantage of m-mode techniques continue to expand For example, color

m-mode echocardiography evolved in the 1990s to provide rapid

evalu-ation of time-related events, such as diastolic mitral regurgitevalu-ation, and

has also been used to provide less load-dependent information regarding

diastolic function Color m-mode techniques have also been applied to

the assessment of myocardial deformation or strain, in which a curved

m-mode is traced along an area of interest of the myocardium and

infor-mation is displayed in both parametric and graphic format, allowing

sensitive evaluation of normal and abnormal patterns of ventricular

con-tractility M-mode images of the left ventricle are often displayed

simulta-neously during left ventricular strain analysis to improve interpretation of

the curves with respect to the cardiac cycle Although m-mode

echocar-diography has been around for a long time and the field of

echocardiog-raphy has dramatically changed with numerous technological advances,

m-mode recordings can still oftentimes provide additional and

comple-mentary information, resulting in a more accurate and complete

echocar-diographic assessment of the heart

This chapter provides case examples of normal m-mode exams, as well

as a diverse spectrum of abnormal m-mode exams illustrating classic

car-diac anomalies Each figure legend provides a “clinical pearl” highlighting

important concepts involved in either technically obtaining or

interpret-ing each m-mode image

NORMAL M-MODE MEASUREMENTS

Normal M-Mode Examination of the Aortic

Root, Aortic Cusp Separation, and Left

Atrial Dimension

Traditionally, m-mode measurements have been used to quantify aortic

root size, aortic valve cusp separation, and left atrial dimensions These

measurements are obtained from the parasternal long-axis imaging plane By convention, m-mode measurements are made leading edge

to leading edge, which differs from two-dimensional measurements, which are made inner edge to inner edge The m-mode cursor is placed perpendicular to the structure being measured Fig 2.4 illustrates the proper m-mode technique for measuring the aortic root, aortic valve cusps, and left atrium The aortic root is measured in end-diastole, just before the onset of the QRS complex The aortic valve cusp separa-tion is measured in midsystole The normal appearance of the aortic cusps during systole is that of an “open box,” which reflects holosystolic opening of the valve leaflets By convention, the left atrium is mea-sured during ventricular systole or atrial diastole, when the left atrium

is maximally filled with blood

Normal M-Mode Examination of the Left Ventricle

The m-mode examination of the left ventricle is also obtained from the parasternal long-axis imaging plane By convention, left ventricular dimensions are made at end-diastole and end-systole, whereas measure-ments of left ventricular wall thicknesses, including the interventricular septum and posterior wall of the left ventricle, are usually measured only at end diastole By convention, the m-mode cursor is placed per-pendicular to the long axis of the left ventricle at the level of the mitral valve chordae Fig 2.5 illustrates the proper m-mode technique for measuring left ventricular internal dimensions at end systole and end diastole, as well as septal and posterior wall thicknesses in end dias-tole In the absence of left ventricular regional wall motion abnormali-ties, m-mode recordings of the left ventricle have been shown to be

an accurate method for calculating left ventricular ejection fraction via the method of Teicholtz According to this method, the left ventricular dimension in diastole squared minus the left ventricular dimension in systole squared is divided by the left ventricular dimension in diastole squared

Normal M-Mode Examination of the Mitral Valve

The normal m-mode recording of the mitral valve—like that of the aortic root, left atrium, and left ventricle—is also obtained from the parasternal long-axis imaging plane The m-mode cursor is placed perpendicular to the long axis of the left ventricle at the level of the tips of the mitral leaflets The anterior leaflet and posterior leaflet are noted to open fully in diastole and close completely during systole (Fig 2.6)

Normal M-Mode Examination of the Pulmonic Valve

The normal m-mode recording of the pulmonic valve is usually obtained from the parasternal short-axis view, but it can also be obtained from the right ventricular outflow tract view and main pul-monary artery and bifurcation view (Fig 2.7) Like the normal aortic valve, the normal pulmonic valve opens throughout systole and has the appearance of “an open box.” Normal m-mode letter designations for the pulmonic valve are as follows: a = atrial contraction, b = onset

of ventricular systole, c = ventricular ejection, d = during ventricular ejection, and e = end of ventricular ejection

M-Mode Imaging

Judy R Mangion

2

M-Mode Imaging

17

2

FIG 2.1 This figure provides an overall view of the strengths of m-mode echocardiography as a diagnostic tool, including superior temporal resolution, which allows for more

precise measurements, and timing of motion of cardiac structures with respect to the cardiac cycle AC, Aortic valve closure; AML, anterior mitral leaflet; EDV, end diastolic ume; ESV, end systolic volume; LV, left ventricle; MO, mitral valve opening; PLAX, parasternal long axis; PML, posterior mitral leaflet (Courtesy of Bernard E Bulwer, MD, FASE.)

vol-Normal M-Mode Examination of the Tricuspid

Valve

The normal m-mode recording of the tricuspid valve is obtained from the

right ventricular inflow view (Fig 2.8) Usually, only the anterior leaflet

of the tricuspid valve is transected by the m-mode cursor M-mode letter

designations for the tricuspid valve are as follows: D = onset of diastole, E

= maximal opening of the leaflet, F = most posterior position of the

leaf-let, E–F slope = closing motion of the leafleaf-let, A = leaflet reopening with

atrial contraction, and C = leaflet closure following ventricular systole

M-MODE ECHOCARDIOGRAPHY IN THE

IDENTIFICATION OF ABNORMAL CARDIAC

STRUCTURE AND FUNCTION

Bicuspid Aortic Valve

M-mode echocardiography can often be useful in helping establish the

diag-nosis of a bicuspid aortic valve (Fig 2.9) The classic appearance of a

bicus-pid aortic valve on m-mode echocardiography is eccentric closing of the

valve leaflets If present, this is strongly suggestive of a bicuspid aortic valve,

although in some cases, bicuspid aortic valves may open symmetrically

Subaortic Membrane

M-mode echocardiography can also be helpful in confirming the

diag-nosis of a fixed subaortic membrane (Fig 2.10) In this case, an m-mode

cursor placed through the aortic valve leaflets will demonstrate early closure of the leaflets in systole In this case, the subaortic membrane decreases the pressure differential between the systemic circulation and left ventricle, causing the aortic valve to close early

Mitral Valve Prolapse

M-mode echocardiography has also been used to diagnose mitral valve prolapse (Fig 2.11) An m-mode cursor placed at the tip of the mitral leaflets in the parasternal long-axis view can demonstrate late systolic pro-lapse of the mitral leaflets into the left atrium Because of the dependence

of the ultrasound beam, however, mitral valve prolapse can be missed

or overdiagnosed with m-mode echocardiography alone For this reason, the diagnosis of mitral valve prolapse be confirmed by two-dimensional methods, which should demonstrate systolic prolapse of greater than 2

mm beyond the plane of the mitral annulus and into the left atrium

Systolic Anterior Motion of the Mitral Valve

M-mode echocardiography is especially useful for establishing the ence of systolic anterior motion (SAM) of the mitral valve, causing dynamic left ventricular outflow tract obstruction (Fig 2.12) This is often seen in the setting of hypertrophic obstructive cardiomyopathy; however, it can also occur in the absence of hypertrophic cardiomyopathy

pres-In the parasternal long-axis view, as the left ventricular chamber decreases

in systole, the anterior cusp of the mitral valve comes into forceful contact

with the protruding interventricular septum The m-mode recording is

especially useful in providing information pertaining to the timing of the

SAM of the mitral valve (i.e., early systolic, holosystolic, or late systolic)

Severe Aortic Insufficiency (Austin

Flint Murmur)

M-mode echocardiography can also provide clues with respect to quantifying

the severity of aortic insufficiency In cases of severe aortic insufficiency, the

aortic regurgitant jet can impinge on the anterior leaflet of the mitral valve,

causing diastolic fluttering as well as early closure of the anterior leaflet of the

mitral valve (Figs 2.13–2.15), or the so-called Austin Flint murmur heard on

clinical exam, which can be mistaken for the murmur of mitral stenosis In

cases of severe acute aortic insufficiency, a sudden increase in diastolic volume

overload causes increased resistance by the ventricle to diastolic filling,

result-ing in early diastolic closure of the mitral valve

Valvular Vegetations

Because of its higher frame rates (i.e., number of times per second the

image is updated on ultrasound), m-mode echocardiography can

some-times identify vegetations that may be missed with two-dimensional

echocardiography M-mode echocardiography may demonstrate the ence of a mobile mass on one of the valves with independent motion (Fig 2.16), which is highly suspicious for vegetation in patients with a strong clinical suspicion of endocarditis

pres-Rheumatic Mitral Valve Deformity

M-mode imaging can also be helpful in establishing the diagnosis of rheumatic mitral stenosis (Fig 2.17) In this case there is reduced open-ing of the mitral leaflets during diastole due to fusion of the commis-sures When used in combination with spectral Doppler of the mitral valve to measure gradients, pressure half-time–derived mitral valve areas, and direct planimetry of the mitral valve area, the added information pro-vided by m-mode can often assist in making a more accurate judgment

as to the severity of mitral stenosis, particularly when there are discrepant data

Cardiomyopathy and Elevated Left Ventricular Filling Pressures

The m-mode examination of the mitral valve can also provide insight into hemodynamics in patients with cardiomyopathy A classic m-mode

FIG 2.2 This figure illustrates the most common m-mode measurements obtained from the parasternal long-axis view, including measurements of the aortic root, cusp tion of the aortic valve leaflets, mitral valve opening and closure, and left ventricular measurements including internal dimensions in diastole and systole and septal and posterior

separa-wall thickness in end-diastole (Courtesy of Bernard E Bulwer, MD, FASE.)

M-Mode Imaging

19

2

FIG 2.3 With m-mode echocardiography, the strength of the reflecting echo structure is demonstrated by the brightness of the image on the ultrasound screen Time is represented

in milliseconds; with respect to the cardiac cycle (systole and diastole), it is displayed on the horizontal axis Distance of the reflecting cardiac structure is displayed on the vertical axis

EDV, End diastolic volume; IVS, interventricular septum; LV, left ventricle; PSAX, parasternal short axis; PW, posterior wall; RV, right ventricle (Courtesy of Bernard E Bulwer, MD, FASE.)

FIG 2.4 Normal m-mode examination of the aortic root, aortic valve cusps, and

left atrium Measurements are obtained in the parasternal long-axis imaging plane

Note the holosystolic opening of the aortic valve cusps By convention, m-mode

mea-surements are made leading edge to leading edge, which differs from

two-dimen-sional measurements The m-mode cursor is placed perpendicular to the aortic valve

leaflets Ao, Aorta; AoR, aortic root; AV, aortic valve; Cusp, aortic leaflet separation;

LA, left atrium; Root, aortic root.

FIG 2.5 Normal m-mode examination of the left ventricle obtained from the nal long-axis imaging plane Left ventricular dimensions are made at end diastole and end systole, whereas septal and posterior wall thicknesses are usually measured only at end diastole The m-mode cursor is placed perpendicular to the long axis of the left ventricle at

paraster-the level of paraster-the mitral valve chordae Ao, Aorta; AV, aortic valve; EDV, end diastolic volume;

EF, ejection fraction; ESV, end systolic volume; FS, fractional shortening; IVS, interventricular

septum; LVIDd, left ventricular internal dimension in diastole; LVIDs, left ventricular internal dimension in systole; LVPWD, left ventricle posterior wall diastole; PW, posterior wall.

para-(arrow) If present, this may be an important clue in establishing the diagnosis of

bicuspid aortic valve In some situations, bicuspid aortic valves may open

symmetri-cally ant, Anterior; pos, posterior.

FIG 2.10 M-mode examination of the aortic valve demonstrating early systolic

closure of the leaflets (arrows) due to a fixed subaortic membrane The membrane

decreases the pressure differential between the systemic circulation and left ventricle,

causing the aortic valve to close early This image was obtained with a

transesopha-geal probe from a longitudinal view of the aortic valve.

FIG 2.11 M-mode examination of the mitral valve demonstrating classic late systolic

bileaflet mitral valve prolapse (arrows); the image was obtained from the parasternal

long-axis view Because of dependence on the ultrasound beam, prolapse can be missed

or overdiagnosed with m-mode echocardiography alone; therefore the diagnosis needs to be confirmed by two-dimensional methods, demonstrating systolic prolapse

of greater than 2 mm beyond the plane of the mitral annulus and into the left atrium.

FIG 2.6 Normal m-mode examination of the mitral valve leaflets from the

para-sternal long-axis imaging plane The m-mode cursor is placed perpendicular to the

long axis of the left ventricle at the level of the tips of the mitral leaflets AL, Anterior

leaflet; PL, posterior leaflet.

FIG 2.7 Normal m-mode examination of the pulmonic valve obtained from the parasternal short-axis view This recording may also be obtained from the parasternal right ventricular outflow view and the main pulmonary artery and bifurcation view Note the holosystolic opening of the cusps, similar to the aortic valve Often, m-mode

of the pulmonic valve only transects the right posterior leaflet In this example, both the anterior and right posterior leaflets are transected The m-mode letter designations for

the pulmonic valve are as follows: (a), atrial contraction; (b), onset of ventricular systole;

(c), ventricular ejection; (d), during ventricular ejection; (e), end of ventricular ejection.

FIG 2.8 Normal m-mode examination of the tricuspid valve obtained from the

right ventricular inflow view Usually only the anterior leaflet of the tricuspid valve

is transected RA, Right atrium; RV, right ventricle; TV, tricuspid valve The m-mode

letter designations for the tricuspid valve are as follows: (D), onset of diastole; (E),

maximal opening of the leaflet; (F), most posterior position of the leaflet; (E–F slope),

closing motion of the leaflet; (A), leaflet reopening with atrial contraction; (C), leaflet

closure following ventricular systole.

M-Mode Imaging

21

2

FIG 2.12 M-mode examination of the mitral valve, parasternal long-axis view,

demonstrating systolic anterior motion of the mitral valve (arrows), which is causing

dynamic obstruction of the left ventricular outflow tract This is often observed in the

setting of hypertrophic obstructive cardiomyopathy However, it can also occur in the

absence of hypertrophic cardiomyopathy In the setting of hypertrophic obstructive

cardiomyopathy, the anterior cusp of the mitral valve comes into forceful contact

with the protruding interventricular septum as the left ventricular chamber decreases

in systole The m-mode recording provides information pertaining to the timing of

systolic anterior motion of the mitral valve.

FIG 2.13 M-mode examination of the mitral valve, parasternal long-axis view,

demonstrating high-frequency diastolic fluttering of the anterior mitral leaflet (arrows)

due to severe aortic insufficiency This is the equivalent of the Austin Flint murmur.

FIG 2.14 M-mode examination of the mitral valve, midesophageal two-chamber

view, also demonstrating high-frequency diastolic fluttering of the anterior mitral

valve leaflet (arrow) due to severe aortic insufficiency, impinging on the leaflet.

FIG 2.15 M-mode examination of the mitral valve, parasternal long-axis view,

demonstrating early diastolic closure of the mitral valve (arrows) due to severe acute

aortic insufficiency The sudden increase in diastolic volume overload causes increased resistance by the ventricle to diastolic filling, causing early diastolic closure of the mitral valve.

FIG 2.16 M-mode examination of the mitral valve demonstrating a large

mobile mass with independent motion on the atrial surface of the posterior leaflet

in a patient with suspected endocarditis (arrow) Because of its higher frame rates,

m-mode echocardiography can sometimes identify vegetations that may be missed

with two-dimensional echocardiography.

FIG 2.17 M-mode examination of the mitral valve affected by rheumatic valvular heart disease There is reduced opening of the mitral valve leaflets during diastole

(arrows) due to fusion of the commissures.

finding in patients with dilated cardiomyopathy is the “b-notch” on the

anterior mitral valve leaflet (Fig 2.18) Although not always present, the

b-notch, when identified, is indicative of a markedly elevated left

ven-tricular end-diastolic pressure

Cardiomyopathy and Reduced Left Ventricular

Ejection Fraction

M-mode interrogation of the mitral valve has also been commonly used

to estimate left ventricular ejection fraction in patients with global left

ventricular systolic dysfunction The m-mode examination in this case

will demonstrate an enlarged E point septal separation (EPSS) (Fig

2.19) This is due to a reduced stroke volume with poor left ventricular

systolic function In general, a normal EPSS should be less than 1 cm

The greater the EPSS distance on m-mode, the worse the overall left

ven-tricular systolic function

Left Ventricular Dyssynchrony

M-mode interrogation of the left ventricle has also been used to establish

the presence of left ventricular dyssynchrony in patients with heart

fail-ure being considered for cardiac resynchronization therapy (CRT) Fig

2.20 illustrates an m-mode recording of the left ventricle in a patient

with left bundle branch block (LBBB) In this patient, there is marked

paradoxical septal motion or delayed contraction of the interventricular

septum in systole Measurement of the septal-to-posterior wall motion

delay (SPWMD), which is defined as the distance between the timing of septal and posterior wall contraction, has been used to predict a positive response to CRT therapy, with greater than 130 ms being used as the cutoff to predict a positive response to CRT

Constrictive Pericarditis

M-mode interrogation of the left ventricle can also be helpful in detecting

an exaggerated respiratory variation of the position of the lar septum (“septal bounce”) (Fig 2.21) Although this is a nonspecific finding in suspected constrictive pericarditis, its identification, along with

interventricu-a strong clinicinterventricu-al suspicion of cinterventricu-ardiinterventricu-ac constriction, should winterventricu-arrinterventricu-ant interventricu-tional directed comprehensive two-dimensional and Doppler evaluation for other markers of cardiac constriction

addi-Cor Pulmonale

M-mode examination of the left ventricle can also be helpful in fying echocardiographic evidence of right heart failure or cor pulmonale complicated by evidence of both pressure and volume overload of the right ventricle (Fig 2.22) M-mode interrogation can readily identify both sys-tolic and diastolic flattening of the interventricular septum (the “D-shaped

identi-septum”) Systolic flattening of the septum represents pressure overload of

the right ventricle from pulmonary hypertension, whereas diastolic ing of the septum represents volume overload of the right ventricle, which

flatten-is often secondary to severe wide-open tricuspid insufficiency

FIG 2.18 M-mode examination of the mitral valve demonstrating a “b-notch” on

the anterior mitral valve leaflet (arrows) in a patient with a dilated cardiomyopathy

Although not always present, the b-notch, when identified, is indicative of markedly

elevated left ventricular end-diastolic pressure.

FIG 2.19 M-mode examination of the mitral valve demonstrating enlarged

E-point septal separation (EPSS) (arrows) in a patient with dilated cardiomyopathy

due to a reduced stroke volume with poor systolic function In general, a normal EPSS

should be less than 1 cm EPSS on m-mode can provide a useful marker of overall left

ventricular systolic function.

FIG 2.20 M-mode examination of the left ventricle, parasternal long-axis view,

in a patient with left bundle branch block Note the paradoxical septal motion, or

delayed contraction of the interventricular septum in systole (arrows).

FIG 2.21 M-mode examination of the left ventricle, parasternal long-axis view, demonstrating exaggerated respiratory variation of the position of the interventricular

septum (“septal bounce”) (arrows) This is a nonspecific finding in suspected

constric-tive pericarditis If clinical suspicion of cardiac constriction is high, it should warrant additional directed comprehensive two-dimensional and Doppler evaluation.

M-Mode Imaging

23

2

FIG 2.22 M-mode examination of the left ventricle, parasternal long-axis view, in

a patient with severe cor pulmonale, demonstrating both systolic and diastolic

flatten-ing of the interventricular septum (“ D-shaped septum”) (arrow) Systolic flattening of

the septum represents pressure overload of the right ventricle from pulmonary

hyper-tension, while diastolic flattening of the septum represents volume overload of the

right ventricle Here, this was secondary to severe wide-open tricuspid insufficiency.

Severe Pulmonary Hypertension

M-mode examination of the pulmonic valve from the parasternal

short-axis or main pulmonary artery view can also assist in identifying the

pres-ence of severe pulmonary hypertension (Fig 2.23) This can be readily

identified by demonstrating early systolic closure of the pulmonic valve

(“flying w”) associated with severe pulmonary hypertension and due to

the elevated filling pressure of the right ventricle Often there may also be

an absent a wave (atrial wave) of the m-mode tracing as well

Ebstein Anomaly

Ebstein anomaly is a congenital deformity characterized by downward

displacement of part or all of the tricuspid valve into the right ventricular

cavity M-mode examination of the tricuspid valve from the right

ven-tricular inflow view can be helpful in establishing the diagnosis of Ebstein

anomaly (Fig 2.24) Typically there is decreased diastolic opening of the

anterior leaflet due to deformation (compare with Fig 2.8, a normal

m-mode view of the tricuspid valve)

Increased Right Atrial Pressure

An elevation in right atrial pressure—seen in different cardiac

patholo-gies including cardiac tamponade, cardiac constriction, and both left- and

right-sided heart failure—can be confirmed by an m-mode tracing of the

inferior vena cava near its communication with the right atrium Fig 2.25

illustrates an m-mode examination of the inferior vena cava obtained in

the subcostal view in the presence of markedly elevated right atrial sure Note the markedly dilated (greater than 2 cm) and plethoric (no

pres-inspiratory collapse) inferior vena cava (IVC) (arrows) The m-mode

cur-sor is placed at the junction of the inferior vena cava and right atrium The estimated right atrial pressure in this scenario is at least 20 mm Hg

In situations of low filling pressures, m-mode recordings of the IVC can confirm greater than 50% inspiratory collapse of the IVC

M-Mode Examination of Prosthetic Valves

M-mode recordings can also be useful in differentiating various types of prosthetic valves, particularly when patients are unaware of the type of valve they may have M-mode can differentiate single-disk, bileaflet, and ball-in-cage mechanical valves and bioprosthetic valves It can also confirm normally functioning prosthetic valves from those with evidence of valve dysfunction Fig 2.26 illustrates an m-mode examination of a normally functioning St Jude bileaflet mechanical aortic valve prosthesis; it was obtained with transesophageal echocardiography from a midesophageal longitudinal view demonstrating opening of both prosthetic valve leaflets in

systole (arrows) Fig 2.27 illustrates a transthoracic m-mode examination of

a normally functioning St Jude bileaflet mechanical mitral valve prosthesis;

it was obtained from the parasternal long-axis view, demonstrating opening

of both prosthetic valve leaflets in diastole (arrows).

FIG 2.23 M-mode examination of the pulmonic valve, main pulmonary artery view,

demonstrating early systolic closure of the pulmonic valve (“flying w”) (arrows) associated

with severe pulmonary hypertension and due to the elevated filling pressure of the right

ventricle Often there may also be an absent a wave (atrial wave) of the m-mode tracing.

FIG 2.24 M-mode examination of the tricuspid valve, right ventricular inflow view,

in Ebstein anomaly Note the decreased diastolic opening of the anterior leaflet due to

deformation (arrow); compare with Fig 2.8, showing a normal m-mode view of the

tricuspid valve The Ebstein anomaly is a congenital deformity characterized by ward displacement of part or all of the tricuspid valve into the right ventricular cavity.

down-FIG 2.25 M-mode examination of the inferior vena cava, subcostal view, in the presence of markedly elevated right atrial pressure (such as tamponade, constriction,

or cor pulmonale) Note the markedly dilated (greater than 2 cm) and plethoric (no

inspiratory collapse) inferior vena cava (arrows) The m-mode cursor is placed at the

junction of the inferior vena cava and right atrium The estimated right atrial pressure

in this scenario is at least 20 mm Hg.

FIG 2.26 M-mode examination of a normally functioning St Jude bileaflet

mechanical aortic valve prosthesis, longitudinal view, obtained with transesophageal

echocardiography To demonstrate correct motion of both prosthetic valve leaflets in

systole (arrows), m-mode echocardiography continues to be an important part of the

evaluation of prosthetic valve function.

FIG 2.27 M-mode examination of a normally functioning St Jude bileaflet

mechanical mitral valve prosthesis, parasternal long-axis view To demonstrate correct

motion of both prosthetic valve leaflets in diastole (arrows), m-mode

echocardiogra-phy continues to be an important part of the evaluation of prosthetic valve function.

Color M-Mode Echocardiography

Color m-mode echocardiography is an ideal modality for confirming the

timing of events with respect to the cardiac cycle, which can be especially

useful in valvular regurgitant lesions Color m-mode has also been used in

the assessment of left ventricular diastolic function and is thought to be less

pre- and afterload-dependent than spectral Doppler In this situation, the

initial propagation velocity (Vp) of blood flow in the left ventricle is

mea-sured Fig 2.28 illustrates a color m-mode examination of the aortic root

and left atrium from the parasternal long-axis view in a patient with mild

diastolic mitral regurgitation (arrow) attributable to heart block Fig 2.29

illustrates a color m-mode examination of the left ventricle, from the apical

four-chamber view, demonstrating a normal Vp of blood flow in the left

ventricle of 81.6 cm/s during diastole, which indicates a normal diastolic

filling pattern Normal propagation velocities are measured by the initial

slope of the E wave on color m-mode and are always greater than 45 cm/s

To make these color m-mode recordings, the Nyquist color scale is moved

up to 39.4 cm/s (arrow), allowing color Doppler flow to be visualized all

the way from the base of the mitral annulus to the left ventricular apex

Fig 2.30 illustrates a color m-mode examination of the left ventricle from

the apical four-chamber view, demonstrating a diastolic filling pattern

consistent with impaired left ventricular relaxation In this case, the Vp

measures 40.2 cm/s and is mildly reduced Fig 2.31 demonstrates a color

m-mode examination of the left ventricle from the apical four-chamber

view, showing a diastolic filling pattern consistent with markedly delayed

propagation or restrictive physiology In this example, the Vp measured

significantly less than 45 cm/s (blue arrow) Note that the accuracy of

the measurement of the Vp of early diastolic filling on color m-mode is

improved by increasing the sweep speed to 100 mm/s (yellow arrow).

Strain Imaging of the Myocardium (Parametric M-Mode Echocardiography)

Strain imaging represents a load-independent technology, now well dated, for measuring regional myocardial deformation of the ventricular myocardium; this is measured in terms of percent to reflect the relative shortening of the myocyte during systole Fig 2.32 illustrates a para-metric curved m-mode examination of the left ventricle from the api-cal four-chamber view demonstrating a normal strain pattern of the left ventricle In this example, a curved m-mode line is traced along the inter-ventricular septum from apex to base The wide orange band in systole represents shortening, whereas the wide yellow band in diastole represents lengthening The four red curves below the parametric image represent

vali-four separate strain measurements from apex to base, with the apex (top

curve) showing the least amount of strain or deformation during systole (arrow) Different strain patterns have been shown to differentiate various

cardiomyopathies, including cardiac amyloidosis as well as hypertrophic

FIG 2.28 Color m-mode examination of the aortic root and left atrium,

para-sternal long-axis view, in a patient with mild diastolic mitral regurgitation (arrow)

attributable to heart block This demonstrates that m-mode echocardiography is an ideal modality for confirming the timing of events with respect to the cardiac cycle.

FIG 2.29 Color m-mode examination of the left ventricle, apical four-chamber view, demonstrating normal propagation velocity of blood flow in the left ventricle

of 81.6 cm/s during diastole, which is indicative of a normal diastolic filling pattern Normal propagation velocities are measured by the initial slope of the E wave on color m-mode and are always greater than 45 cm/s Note that the Nyquist color scale

is moved up to 39.4 cm/s (arrow), allowing color Doppler flow to be visualized all the

way from the base of the mitral annulus to the left ventricular apex.

to reflect the relative shortening of the myocyte during systole In this example, a curved m-mode line is traced along the interventricular septum from apex to base The wide

orange band in systole represents shortening, whereas the wide yellow band in diastole represents lengthening The four red curves below the parametric image represent four

separate strain measurements from apex to base, with the apex (top curve) showing the least amount of strain or deformation during systole (arrow).

FIG 2.30 Color m-mode examination of the left ventricle, apical four-chamber

view, demonstrating a diastolic filling pattern consistent with impaired left ventricular

relaxation In this case, the propagation velocity measures 40.2 cm/s and is mildly

reduced Color m-mode in a useful tool in the assessment of diastolic function of the

left ventricle and is thought to be less flow-dependent than pulsed-wave Doppler.

FIG 2.31 Color m-mode examination of the left ventricle, apical four-chamber view, demonstrating a diastolic filling pattern consistent with markedly delayed prop- agation or restrictive physiology In this example the propagation velocity measured

significantly less than 45 cm/s (blue arrow) Note that the accuracy of the

measure-ment of the propagation velocity of early diastolic filling on color m-mode is improved

by increasing the sweep speed to 100 mm/s (yellow arrow).

I and hypertensive cardiomyopathies This is an exciting and active area of investigation in the field of echocardiography that is likely to significantly

improve the diagnostic capabilities of cardiac ultrasound in the future

SUMMARY

M-mode echocardiography, because of its superior temporal resolution,

remains important in today’s echo lab because of its ability to time

rap-idly moving structures within the heart, such as the valves, in relation to

the cardiac cycle It is capable of providing additional clues to answering

complex clinical questions, and represents an inexpensive tool, in the vast and widely expanding echocardiography tool box

INTRODUCTION

Contrast echocardiography is a broad term used to describe an array of

approaches that can be used to improve and expand diagnostic

capabili-ties by acoustic enhancement of the blood pool during cardiac

ultra-sound imaging.1,2 Ultrasound contrast agents are generally composed

of gas-filled encapsulated microparticles, usually microbubbles that

are 1–5 μm in diameter, or nanoparticles.1 The most common clinical

application of contrast echocardiography has been to better delineate

the endocardial contours of the left ventricular (LV) cavity, termed left

ventricular opacification (LVO; Fig 3.1).3,4 Although there are many

reasons clinicians opt for performing LVO in a given patient, the most

frequent indication is to better evaluate global or regional LV systolic

function (Videos 3.1 and 3.2) Justification for this application of LVO

is based on (1) the inability to fully examine LV myocardial thickening

in 10%–20% of unselected patients; (2) the frequent use of echo to

guide management in critically ill patients who have difficult acoustic

windows due to positive pressure ventilation or inability to cooperate

with the ultrasound examination; and (3) frequent use of echo to make

critical decisions based on the presence of segmental wall motion, where

every myocardial segment needs to be well seen with a high degree of

reader confidence (e.g., stress echocardiography, point-of-care echo for

detection of myocardial ischemia or evaluation of heart failure) There

are many other clinical situations where LVO has had a positive impact

in clinical echocardiography (Box 3.1)

Refinements in contrast ultrasound technology that improve the

detection of microbubble signal in the coronary circulation relative to

myocardial tissue signal have permitted the imaging of the myocardial

microcirculation These techniques are broadly referred to as

myocar-dial contrast echocardiography (MCE) The most basic approach to

MCE is to spatially evaluate the presence of an intact microcirculation

The presence of a functional microvascular bed can be used to assess

myocardial viability, to characterize a cardiac mass as a tumor rather

than thrombus based on the presence of functional microvessels, and

to detect therapeutic or spontaneous reperfusion in acute myocardial

infarction (Fig 3.2; Videos 3.3–3.5).5–10 Quantitative or

semiquan-titative assessment of perfusion requires not only quantification of

the intact microvasculature but also temporal information of

micro-bubble transit through the microcirculation This measurement

gen-erally requires destruction of microbubbles within the acoustic sector

and evaluation of signal reappearance.11 This approach can be used to

detect resting ischemia, flow heterogeneity during stress

echocardiogra-phy, or microvascular dysfunction, or to assess the presence/adequacy

of collateral blood flow

In this chapter, the basic principles of contrast echocardiography will

be described, including an overview of contrast agents and the specific

imaging modalities that have been developed to improve microbubble

signal-to-noise ratio during clinical imaging Clinical applications of

con-trast echocardiography are detailed in Chapter 12

MICROBUBBLE CONTRAST AGENTS

Signal enhancement during contrast echocardiography relies on the

dynamic interaction of ultrasound pressure waves, with a highly

compressible and expandable particle that is smaller in scale than the

wavelength of ultrasound applied As will be described later, particle

expansion and compression during ultrasound pressure peaks and

nadirs, respectively, produces volumetric oscillations of these particles,

which is the primary source of ultrasound signal generation.12–14 The

rationale for using microbubbles, as ultrasound contrast agents is based

on their compressibility/expandability, and on their in vivo stability Air and high-molecular-weight gases that have been used in micro-bubble contrast agent preparations are several orders of magnitude more compressible than water or tissue During most forms of clini-cal contrast echocardiography, contrast oscillation and the subsequent acoustic energy response occurs for particles that are resident within the vascular compartment of interest (e.g., the LV cavity or myocardial microcirculation)

The initial description of contrast enhancement by microbubbles was made by Gramiak and Shah, when a cloud of echo signals was detected

in the right heart, coming from the formation of microbubbles formed

by fluid dynamic forces during rapid, high-pressure intravenous tion of a water-soluble fluorophore used at the time for measurement

injec-of cardiac output during heart catheterization.15 Over the ensuing years, several different forms of nonencapsulated microbubbles generated by hand agitation or low-frequency sonication were investigated, including for myocardial enhancement by MCE after intracoronary injection.16–19

These techniques were limited by the wide range of microbubble sizes produced, the inability of most of these microbubbles to pass to the left heart after intravenous injection, and the potential for large bubbles to become entrapped within the microcirculation when given as an intra-arterial injection

The safety, reproducibility, and widespread clinical feasibility of ducing LV cavity and myocardial opacification with intravenous contrast administration microbubble contrast agents relied on the advent of small but stable and acoustically active microbubbles that are able to pass freely through pulmonary and systemic capillaries.1 Many of these microbubble agents also have a relatively narrow size distribution (relatively mono-disperse).20 Those that do not, termed polydisperse agents, still contain

pro-relatively few microbubbles that are greater than the average functional capillary diameter of 5–7 μm when taking into account intraluminal pro-jection of the glycocalyx.21,22 The creation of these stable size-controlled microbubbles that produce a strong acoustic signal relied on two major modifications: (1) a change in the gases used for the microbubble core material, and (2) microbubble encapsulation

A partial list of some of the microbubble contrast agents that are currently commercially produced, marketed, and used in patients are shown in Fig 3.3 One of the common features of these agents is that the gas core is not composed of ambient atmospheric air components, which are for the most part nitrogen and oxygen The reason for this compositional modification is based on mathematical models that have been used to predict the stability of a gas bubble The rate of disappear-ance for a gas bubble in any given medium is dependent on the bubble size, the surface tension, and constants that describe the solubility and diffusion capacity of the gas in the bubble.23 Accordingly, the stability

of microbubble contrast agents used in humans is improved when they contain gases with low diffusion coefficients and low solubility in water

or blood, which is described by the ratio of the amount of gas dissolved

in the surrounding liquid to that in the gas phase, or the Ostwald ficient.24 These gases also must be inert, safe to use in humans, and cleared readily through respiration These requirements are met in con-temporary agents by using high-molecular-weight gases such as perfluo-rocarbons that remain in gas form at room and body temperature—for example, octafluoropropane (C3F8), decafluorobutane (C4F10), or sulfur hexafluoride (SF6)

coef-The encapsulation of the microbubbles represents a second mon feature of contemporary contrast agents On the most basic level, encapsulation with a “shell” composed of biocompatible materials such

com-Principles of Contrast Echocardiography

Jonathan R Lindner

3