Comprehensive Textbook of Echocardiography (2 Volumes) Navin C Nanda
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1HISTORY AND BASICS

History of EchocardiographyCHAPTER 1

Fadi G Hage,
Anant Kharod,
David Daly,
Navin C Nanda
 
INTRODUCTION
The development of echocardiography is an interesting story that traverses three centuries and many continents. From the study of ultrasound waves in bats to Nobel Prize winners in physics, to increased military interest in ultrasonography due to the Titanic and World War I, to two- (2D) and three-dimensional (3D) echocardiography, the history of echocardiography highlights human ingenuity and perseverance. This started with A-mode still images derived by a thin ultrasound beam and advanced to M-mode (moving) displays (Figs 1.1 and 1.2). Eventually the technology advanced to allow for 2D examination of the heart in motion (Fig. 1.3). This was followed by the addition of conventional Doppler and color Doppler, the recent introduction of tissue Doppler and speckle tracking imaging, contrast echocardiography, transesophageal echocardiography, 3D transthoracic and transesophageal echocardiographic reconstruction, and ultimately the development of real time, 3D echocardiography (Figs 1.4A to D).13
Today, echocardiography is the most frequently utilized imaging modality in cardiology and is at the center of our diagnostic and decision-making algorithms in many, if not most, cardiac pathologies.
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Fig. 1.1: One-dimensional echocardiography (M-mode). The frontal projection of the heart demonstrates the concept that M-mode is equivalent to extraction of a plug of tissue that corresponds to the width of the beam passing through the heart. The removed plug is shown to the right and contains a portion of the right ventricle (RV), ventricular septum (VS), mitral valve (MV), and left ventricular posterior wall (LVW). A schematic of structure motion along with the ECG is included. (ECG: Electrocardiogram).Source: Reproduced with permission from Nanda NC, Gramiak R. Clinical Echocardiography. St. Louis, MO: C. V. Mosby; 1978: 370.
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Fig. 1.2: Nanda pointing to an M-mode echo tracing on the monitor of one of the earliest echo systems manufactured for clinical use (early 1970s).
With current technology, echocardiography can provide useful information regarding cardiovascular structure and morphology, cardiac function, and hemodynamics in a noninvasive, versatile, and portable modality that is relatively inexpensive and safe to the patient and physician. This is partly why echocardiography has been the mainstay in cardiac imaging over the last half a century and promises to keep its throne, at least in the near future, because of continued revolutions in this field that will keep it relevant to the practicing physician in the 21st century.
This chapter highlights several of the key inventions and historical figures in ultrasonography and echocardiography from the past and present, which have made echocardiography the staple in clinical cardiology that it is today.
 
HISTORY OF ULTRASOUND
Ultrasound, defined as a sound wave with a frequency above the limit of normal human hearing, is a natural phenomenon that is abundant in nature. It was first recognized, as early as the 18th century, that bats, although blind, use ultrasound to detect their prey.4 It is also widely appreciated that whales and dolphins use sonar to navigate and hunt. Humans, by definition, cannot hear ultrasound, but there has been a great interest in developing technologies that can detect ultrasound for various applications.
It has been noted that physiotherapists were possibly the first care providers who integrated ultrasound into their practice, using sound as an instrument to treat arthritis and muscle aches.1 In fact, in 1761, Viennese physician Leopold Auenbrugger studied the effects of sound via percussion to diagnose cardiopulmonary problems.1 However, it was the discovery of piezoelectricity in 1880 by Jacques and Pierre Curie that allowed for harnessing the power of ultrasound. Later, Pierre and his wife Marie shared the 1903 Nobel Prize in physics with Antoine Becquerel for the discovery of radioactivity.4 The major stimulus for the development of ultrasound for human use came with the sinking of the Titanic on April 15, 1912, on its maiden voyage when it struck an unseen iceberg. In tandem, there was interest in developing a technology to avert the threat of the German U-boats in sinking allied ships. By 1918, Paul Lavengin, a French physicist, succeeded in developing a sonar system that was capable of producing ultrasound and analyzing returned acoustic echoes.1,4 This led to multiple discoveries that allowed for the use of sonar technology in naval warfare during World War II. After the war, scientists worldwide worked on developing the technology for peaceful purposes.
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Fig. 1.3: Two-dimensional (2D) scanning concept (2D echocardiography). Real time 2D images are equivalent to slices of the heart that are removed and observed in motion. This illustration shows the cardiac cavities and valves viewed in the long axis of the left ventricle and the relationship of this plane to a frontal view of the heart.Source: Reproduced with permission from Nanda NC, Gramiak R. Clinical Echocardiography. St. Louis, MO: C. V. Mosby; 1978: 371.
 
THE DEVELOPMENT OF CLINICAL CARDIAC ULTRASOUND: A-MODE AND M-MODE ECHOCARDIOGRAPHY
The credit for the development of clinical cardiac ultrasound goes mostly to Inge Edler and Hellmuth Hertz.5
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Figs 1.4A to D: Progress in echocardiography. The chronology of the books and video textbooks produced by Nanda illustrate the progressive development of echocardiography from M-mode to two-dimensional, conventional and color Doppler, contrast, and two- and three-dimensional transthoracic and transesophageal echocardiography.
Dr Edler, a cardiologist at the University Hospital in Lund, Sweden, was interested in developing a diagnostic method for evaluating patients with mitral stenosis prior to undergoing surgery and identifying patients who have significant mitral regurgitation, which would preclude them from having surgery.6 For this purpose, he collaborated with Dr Hertz, a physicist who graduated from the same university and was studying ultrasound and its applications. Hertz was well known for hailing from a well-established scientific family since his father, Gustav Hertz, won the Nobel Prize in physics in 1925 for his work on the laws governing the impact of an electron upon an atom and his uncle Heinrich Hertz, in whose honor wave frequencies were named in 1930.
Visiting a company in Mälmö, Hellmuth Hertz initially tested an ultrasound machine on himself. After seeing signals he thought originated from his posterior wall, Hertz agreed to work with Edler and they proceeded to borrow a pulse-echo sonar machine from a shipyard for a weekend in 1953 in order to start their experiments.2 Due to the positive results of their experiment, the manager of the shipyard company agreed to lend them the machine for over a weekend to continue their research.6 Siemens was impressed by their work and lent them a reflectoscope for a year in order to perform their work partly due to Hertz's family connections at the company.1,7 They realized that by using ultrasound they were able to identify the interface between the wall of the heart and its fluid-filled cavity. After studying heart specimens, they proceeded to human studies; it is notable that Hertz's first human volunteer was himself.2 They documented a signal that moved with cardiac movement, which they originally attributed to the movement of the left atrial wall. Edler then proceeded to 6perform “ultrasound cardiography” on patients on their dying bed and carefully documented the site and angle of the ultrasound beam. After the demise of a patient, he would place an ice pick in the direction of the M-mode beam and dissect the heart to identify the structures that the ultrasound beam traversed. Through this elegant approach, he was able to document that the moving signal was actually arising from the anterior mitral leaflet rather than from the posterior wall of the left atrium. Edler then showed his findings in a movie at the European Congress of Cardiology in Rome in 1960 and published several manuscripts pertaining to ultrasound cardiography.56,812 Edler also described the use of the movement of the anterior mitral valve leaflet (E–F slope) for the diagnosis of mitral stenosis and for quantitating its severity. Patients with mitral stenosis had a reduced speed of the diastolic downstroke E–F slope of the anterior mitral leaflet.6
Hertz developed inkjet technology in order to record the cardiograms that they obtained, and he was successful in commercially promoting the use of this new technology for multiple applications.
In the United States, John Reid, at the University of Pennsylvania, built an ultrasonic reflectoscope, and through a collaboration with Dr Claude Joyner, he repeated the work of Edler on mitral stenosis and published the first manuscript on the use of echocardiography in the United States in 1963.13
At the same time, Dr Harvey Feigenbaum was interested in measuring left ventricular volumes and pressures for the assessment of compliance. He attended the American Heart Association meeting in 1963 in order to examine a machine that was advertised to measure cardiac volumes using ultrasound. When he examined the machine at the meeting, it was apparent that it could not deliver that promise, and he was frustrated. Rather than turning away, he examined the instrument on his own heart, and the company salesman explained how the ultrasound signal is produced. Feigenbaum was intrigued and asked what would happen if there was fluid around the heart, and the salesman answered that the fluid should be echo free.2 He thus realized that this technology can be useful for the diagnosis of pericardial effusion.
After returning to Indiana, he borrowed an ultrasound machine from a colleague in neurology, who was using it to detect deviations in the brain caused by intracranial masses, and examined a patient with pericardial effusion and documented the presence of the echo-free space. These observations were then confirmed in the animal laboratory and published in 1965.14
Despite this, there was general skepticism with regard to the clinical utility of echocardiography. Feigenbaum collaborated with Dodge at the University of Alabama in 1968 to develop M-mode echocardiography for the measurement of left ventricular dimensions. However, they were unable to publish their work until years later after their findings were reproduced by other investigators.1517 In the late 1970s, only three cardiac valves—mitral, aortic, and tricuspid—could be identified by echocardiography. It was believed that the pulmonary valve was inaccessible since it was situated beneath the lung tissue. Dr Navin C Nanda who joined the University of Rochester in upstate New York in early 1971 as a cardiology fellow was not convinced that this was true, and during discussions with a pathologist at the autopsy of a cardiac patient, it became clear that the pulmonary valve was not covered by lung in a majority of patients. Subsequently, he, together with Dr Gramiak, was successful in imaging and identifying the pulmonary valve by M-mode echocardiography (Fig. 1.5).18 This discovery essentially resulted in the birth and development of pediatric echocardiography since all four cardiac valves could now be imaged successfully. This made it possible to diagnose many congenital cardiac disease entities such as dextrotransposition of the great vessels.19,20
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Fig. 1.5: Echocardiographic detection and validation of the pulmonary valve. Indocyanine green was injected into the pulmonary artery during cardiac catheterization. The left pulmonary cusp is identified by the dense contrast material filling it. The dense linear bands extending anteriorly during early diastole probably originate in another contrast-filled pulmonary cusp which lies above the plane of study during most of the cardiac cycle. The scattered echoes in front of the left pulmonary cusp are probably in the right ventricular outflow tract as a result of catheter-induced valvular regurgitation. (AV: Aortic valve; ECG: Electrocardiogram; Inj: Injection signal; LA: Left atrium; PCG: Phonocardiogram; PV: Pulmonary valve; RA: Right atrium).Source: Reproduced with permission from Gramiak R, Nanda NC, Shah PM. Echocardiographic detection of the pulmonary valve. Radiology. 1972;102:153–7.
7Nanda remembers often being called in the middle of the night to perform echocardiograms on cyanotic newborns to diagnose or rule out dextrotransposition of the great vessels. Early diagnosis was life saving in these newborns since it resulted in enlarging the patent foramen ovale (PFO) or performing atrial septostomy in the cardiac catheterization laboratory to promote improved mixing of pulmonary and systemic circulations. M-mode echo was also used for the first time to assess pulmonary hypertension21 and diagnose a congenital bicuspid aortic valve22 and evaluate intra-atrial baffle dysfunction in transposition of the great vessels (Figs 1.6 and 1.7).23
In its early development, M-mode echo was most commonly used in a clinical setting to detect pericardial effusion and to diagnose mitral stenosis and assess its severity. This was done by measuring the early diastolic slope of the mitral valve M-mode tracing, and it was shown that the slower the diastolic slope, the more severe the stenosis with good correlations with cardiac catheterization findings. However, when Nanda relooked at this in a large number of patients with M-mode echo and using actual left atrial pressures measured by the trans-septal approach in the cardiac catheterization laboratory, no significant correlation was found. He attempted to publish these findings but was unsuccessful because it was believed that this could “destroy” the emerging technique of echocardiography. He was, however, able to publish it as an abstract.24 Subsequent studies by other investigators supported his findings and the mitral diastolic slope was no longer used to assess the severity of mitral stenosis. Two comprehensive books on M-mode echocardiography, one written by Feigenbaum and the other by Nanda and Gramiak, also helped publicize echocardiography and bring into focus the clinical utility of this noninvasive technique.25,26
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Fig. 1.6: Pulmonary hypertension and right heart failure. The pulmonary valve echo is from a patient with severe pulmonary hypertension complicated by severe right heart failure. A large “a” dip is observed. The valve opens rapidly, and the amplitude of the opening movement is large. The representation of the right ventricular and pulmonary artery pressure tracings was obtained at cardiac catheterization in this patient. The high right ventricular end-diastolic pressure (38 mm) results in a low gradient (4 mm) across the pulmonary valve in diastole (shaded). (ECG: Electrocardiogram; PA: Pulmonary artery pressure tracing; PV: Pulmonary valve echo tracing; RV: Right ventricular pressure tracing. The scale represents pressures in mm Hg).Source: Reproduced with permission from Nanda NC, Gramiak R, Robinson TI, Shah PM. Echocardiographic evaluation of pulmonary hypertension. Circulation. 1974;50:575–81.
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Fig. 1.7: Comparison of normal and bicuspid aortic valve. The aortic root echocardiogram in the upper panel is obtained from a patient with a tricuspid aortic valve. The valve echoes are observed in diastole in the middle of the aortic lumen, and the leaflet images appear symmetric. The lower panel demonstrates an aortic root echogram obtained from a patient with a bicuspid aortic valve. Marked eccentricity of the diastolic cusp signals with respect to the aortic lumen is present. The anterior cusp image is large and practically occupies the whole aortic lumen while the posterior leaflet is miniscule. (AO: Aortic root; ECG: Electrocardiogram; PHONO: Phonocardiogram; RESP: Respirations).Source: Reproduced with permission from Nanda NC, Gramiak R, Manning J, et al. Echocardiographic recognition of the congenital bicuspid aortic valve. Circulation. 1974;49;870–5.
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TWO-DIMENSIONAL ECHOCARDIOGRAPHY
Although M-mode constituted the real birth of clinical echocardiography, there was general skepticism about the future of echocardiography because the interpretation of the images was nonintuitive. The development of 2D echocardiography constituted a revolution in the field unequalled except with the later introduction of 3D echocardiography. The group at the University of Rochester, led by Gramiak, envisioned the reconstruction of the information embedded in the M-mode to develop 2D and ultimately 3D images of the heart in the early 1970s.27 Although the principles and the techniques used were sound, the application was hampered by the slow processing power of the computers available at that time.
Nicolaas Bom of the Netherlands, in 1971, developed the linear array system and was able to visualize moving cardiac images. Bom initially studied electronic engineering and then served in the Navy where he worked with sonar, transducers, and linear array signals. He later graduated from a medical school in Rotterdam and applied his knowledge of sonar to medicine. Having read works by Hertz, Edler, and several others, he realized that their methods were one dimensional and that the majority of the heart could not be visualized with a narrow sound beam. The linear scanner developed by Bom in Rotterdam was the first real time, 2D scanner that was widely available.28 Current 2D systems are based on the work of Griffith and Henry who developed a mechanical handheld device capable of 2D scanning at the National Institutes of Health.29
The development of real time, 2D echocardiography resulted in an explosive growth in the utility of echocardiography, and it was not long before practically every large hospital with cardiology service owned at least one 2D echo system. Among the several clinical applications, some of the first ones from our group included echocardiographic assessment of intracardiac pacing catheters30, pacemaker perforation31,32, pacing-induced thrombosis, and echocardiographic studies done during sustained ventricular tachycardia (Figs 1.8A and B).33,34 The first article elucidating the differentiation of left ventricular pseudoaneurysms from true aneurysms by 2D echocardiography was published in 1980.35 Other studies included 2D echo features of atrial septal aneurysms,36 2D echo diagnosis of right ventricular infarction,37 myocardial texture recognition by 2D echo, and correlation of 2D echo pattern with histopathology of intracardiac masses (Fig. 1.9).3839 The first study demonstrating the currently popular technique of posttreadmill exercise echocardiography in the assessment of coronary artery disease was published from our group in 1981.40 It took almost 8 years before another study was published from our echo laboratory showing its temporal reproducibility.41
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Figs 1.8A and B: Pacing catheter perforation. The subcostal four-chamber view shows the temporary pacing catheter (P) passing through the right ventricular (RV) apex (arrow), with the tip located just beyond the epicardial surface. The echo-free space inferior to the cardiac apex represents a portion of the patient's stomach (S). When the patient swallowed water, contrast echoes appeared in this space, confirming its relationship to the gastrointestinal tract. The prominent echo in the right ventricle originates from a Swan-Ganz catheter (SG). (A: Anterior; AW: Anterior wall; I: Inferior; L: Liver; LA: Left atrium; LV: Left ventricle; MV: Mitral valve; P: Posterior; RA: Right atrium; RB: Reverberation; S: Superior; TV: Tricuspid valve; VS: Ventricular septum).Source: Reproduced with permission from Gondi B, Nanda NC. Real time, two-dimensional echocardiographic features of pacemaker perforation. Circulation. 1981;64:97–106.
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Fig. 1.9: Right ventricular aneurysm due to right ventricular infarction. The right heart apical two-chamber view shows a large aneurysm (AN) that involves the apical region. (A: Anterior; DW: diaphragmatic wall; I: Inferior; L: Left; L: Liver; P: Posterior; R: right; RA: Right atrium; S: Superior).Source: Reproduced with permission from D'Arcy B, Nanda NC. Two-dimensional echocardiographic features of right ventricular infarction. Circulation. 1982;65:167–73.
The first study demonstrating the usefulness of the cold pressor test during real time, 2D echocardiography in the assessment of coronary artery disease came out in 1984.42 The same year saw the publication of a study demonstrating comprehensive evaluation of aortic aneurysm and dissection by 2D echo/conventional Doppler (Figs 1.10 and 1.11).43 Other studies showing the clinical utility of 2D echo in the diagnosis of arrhythmogenic right ventricular dysplasia,44 pulmonary artery branch stenosis,45 and pulmonary artery aneurysms46 were also published in the early 1980s.
 
CONVENTIONAL DOPPLER ULTRASOUND
The Doppler effect is named after the Austrian physicist Christian Doppler who proposed in 1842 that the frequency of a wave to an observer is higher than the emitted frequency if the source is moving toward the observer and lower than the emitted frequency if the source is receding from the observer.47 His theory was ridiculed until it was proved correct 15 years after his death. It was not until 1956 that Dr Satomura, in Japan, first utilized the Doppler theory to examine the movement of cardiac structures.48 In the United States, Rushner in Seattle worked on cardiac Doppler in the 1960s and introduced the technique to Baker,49 who went on to develop the first pulsed Doppler recording device.50 Holen and Hatle then showed how Doppler can be used to derive hemodynamic data using the Bernoulli equation.5153 These measurements proved quite useful for the assessment of mitral and aortic stenosis and popularized the use of Doppler with echocardiography. In the meantime, Baker had sent a Doppler ultrasound to Nanda to investigate. Nanda recalls placing the probe on his own chest and being initially unable to interpret results. He attended a course on Doppler in Seattle conducted by Baker and became “certified” in Doppler during a time in which only a handful of people were certified. Many other applications of conventional Doppler followed including its usefulness in the assessment of coronary arteries and fetal hemodynamics (Fig. 1.12).5456 The first book on Doppler echocardiography was published in 1982 by Drs Hatle and Anderson57 followed by a book from Nanda.58 Nanda remembers being invited to go to China in early 1982 and introducing the pulsed Doppler technique to that country at a time when it was just opening up to foreigners. He was given a letter to this effect from the People's Liberation Army Hospital in Beijing and the Practical Acoustic Association of China, which also stated his lectures had “strengthened the friendship and mutual understanding between USA and China”! Our group was the first to use 2D echo/Doppler in cardiac pacing to maximize cardiac output, minimize mitral regurgitation, and assess atrial capture (Fig. 1.13).59
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Fig. 1.10: Two-dimensional echocardiographic evaluation of the aorta. The aorta reconstructed from the root level to the abdominal region by assembling Polaroid® images of contiguous segments obtained from multiple transducer positions. (AA: Ascending aorta; ABA: Abdominal aorta; CC: Common carotid; IN: Innominate artery; PA: Pulmonary artery; SC: Subclavian; TA: Transverse aorta; TDA: Thoracic descending aorta).Source: Reproduced with permission from Mathew T, Nanda NC. Two-dimensional and Doppler echocardiographic evaluation of aortic aneurysm and dissection. Am J Cardiol. 1984;54:379–85.
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Figs 1.11A and B: Two-dimensional echocardiographic evaluation of aortic aneurysm and dissection. (A) Ascending aortic aneurysm. This composite illustration was made by the reconstruction method to show the full extent of the aneurysm. The transverse arch (T) and the descending aorta (DA) are not involved. (B) Aortic dissection (DeBakey type 1). This composite illustration was also made by the reconstruction method. The dissection flap (arrows) can be seen in the ascending aorta (AA), transverse arch (TA), thoracic descending aorta (TDA), and in the abdominal segment (ABA). (AA: Ascending aorta; V: Aortic valve. AV: Aortic valve; PA: Pulmonary artery).Source: Reproduced with permission from Mathew T, Nanda NC. Two-dimensional and Doppler echocardiographic evaluation of aortic aneurysm and dissection. Am J Cardiol. 1984;54:379–85.
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Fig. 1.12: Typical Doppler power spectra from the umbilical arteries in a normal pregnancy is shown on the left. Doppler power spectra from a pregnancy with premature rupture of membranes and oligohydramnios is depicted on the right.Source: Reproduced with permission from Maulik D, Saini VD, Nanda NC, Rosenzweig MS. Doppler evaluation of fetal hemodynamics. Ultrasound Med Biol. 1982;8: 705.
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Fig. 1.13: Usefulness of Doppler echocardiography in cardiac pacing. Peak aortic flow velocity at different atrioventricular (AV) intervals. +, mitral regurgitation present; ++, increased mitral regurgitation; –, mitral regurgitation not evaluated by Doppler. The number in parenthesis indicates the maximum percentage change in peak aortic flow velocity obtained in a given patient as compared to the VVI value or value at the shortest AV interval (in patients in whom VVI values were not available). Note that the maximum percentage change occurred with pacing at AV intervals between 150 and 200 ms. The initials of each patient are given at the right of each Doppler flow velocity curve.Source: Reproduced with permission from Zugibe FT, Nanda NC, Barold SS, Akiyama T. Usefulness of Doppler echocardiography in cardiac pacing. Assessment of mitral regurgitation, peak aortic flow velocity, and atrial capture. PACE. 1983;6:1350–7.
The incremental value of sequential atrioventricular pacing over regular right ventricular pacing using a prototype continuous-wave Doppler system developed by Dr Henry Light of England was also shown by us.60
11An increase in stroke volume of up to 25% with sequential atrioventricular pacing was demonstrated (Fig. 1.14).
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Fig. 1.14: Doppler echocardiographic studies in sequential AV pacing. In this patient with sequential AV pacing, the Doppler transducer was placed in the suprasternal notch and angled inferiorly and to the left to record blood flow in the proximal descending aorta. The Doppler blood flow patterns (DS) are denoted by triangular waveforms and the height of the triangle represents peak aortic blood flow velocity. When the patient was switched from DVI to VVI mode, a significant decrease occurred in the height and size of the triangles, indicative of significant reduction in the stroke volume and cardiac output (heart rate was kept constant in both pacing modes). The vertical distance between the arrows represents 1 m/s and this scale is common for both VVI and DVI tracings.Source: Reproduced with permission from Nanda NC, Bhandari A, Barold SS, Falkoff M. Doppler echocardiographic studies in sequential atrio-ventricular pacing. PACE. 1983;6:811–14.
 
COLOR DOPPLER ULTRASOUND
Color Doppler flow imaging was developed in the 1980s, which allowed for the visualization of blood flow noninvasively.61 The first commercially available color Doppler echo machines were developed in Japan where Omoto and his group did some of the early work.62 Nanda realized the potential of color Doppler when he was privately shown a “work-in-progress” system during a scientific meeting in Taiwan. Drs John Kirklin and Gerald Pohost at the University of Alabama agreed to buy two color Doppler systems whenever they were commercially available, prompting Nanda to move to Birmingham from Rochester. Color Doppler was first introduced as a clinical tool to the United States in 1984 at the University of Alabama at Birmingham (Fig. 1.15). His group also pioneered the color Doppler assessment and semiquantitation of mitral, aortic, and tricuspid valvular regurgitation in a reliable and reproducible manner (Figs 1.16 and 1.17).6365 Some of the initial work also showed the usefulness of color Doppler as an adjunct to 2D echo in the assessment of aortic dissection, aortic valve stenosis, prosthetic heart valves, and fetal hemodynamics (Fig. 1.18).6669 It was used during supine bicycle exercise to identify the development or worsening of mitral regurgitation as a marker for left main or three-vessel coronary artery disease.70 Color Doppler also began to find application in the evaluation of vessels outside the heart.71 Within only a few years of its introduction, it became an integral part of a clinical echocardiographic examination. Its popularity was further helped by several publications on the subject in the 1980s.7274
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Fig. 1.15: Aloka 880 Color Doppler System. Compliments of Aloka, Tokyo, Japan.
 
CONTRAST ECHOCARDIOGRAPHY
The history of contrast echocardiography dates back to the early days of echocardiography when Joyner noticed the contrast effect using ultrasound following intravenous fluid injection; but, these observations were not published. Gramiak, a radiologist at the University of Rochester, Rochester, New York, borrowed a new ultrasound machine from the cardiology department to try it out. He tested the machine on a patient with aortic regurgitation who was undergoing angiography. During the injection of indocyanine green, he noted the defect in the contrast material caused by the backflow of blood into the ventricle, and Dr Pravin Shah and he developed the technique of contrast echocardiography for the study of the aortic valve and the aortic root.75
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Figs 1.16A and B: Color Doppler assessment of mitral regurgitation. (A) Maximum RJA/LAA% obtained from analysis of all three two-dimensional echocardiographic planes compared with angiography (all 82 patients). (B) Flow acceleration. A simple example of the generation of flow acceleration can be shown by observing the draining of water from a household bathtub. Flow acceleration or a localized area of high velocity develops as the large body of water moves toward the “hole” or opening in the bottom of the tub through which water flows into the drain. Adjacent to the “hole,” the area of flow acceleration becomes smaller and tends to take the shape and size of the circular “hole.” This finding has clinical significance. For example, in a patient with mitral regurgitation, inspection of the size and shape of the flow acceleration present adjacent to the mitral valve (MV) may provide a good estimate of the size of the anatomical defect in the MV through which the regurgitation is occurring. (AF: Atrial fibrillation; LAA: Left atrial area; NSR: Nnormal sinus rhythm; RJA: Mitral regurgitant area).Source: (A) Reproduced with permission from American Heart Association, Helmcke F, Nanda NC, Hsiung MC, et al. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation. 1987;75:175–83.Source: (B) Reproduced with permission from Nanda NC. Atlas of Color Doppler Echocardiography. Philadelphia, PA: Lea & Febiger; 1989:7.
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Fig. 1.17: Demonstration of the usefulness of tricuspid valve annulus measurement and color Doppler flow mapping for the assessment of tricuspid regurgitation.Source: Reproduced with permission from Chopra HK, Nanda NC, Fan P, et al. Can two-dimensional echocardiography and Doppler color flow mapping identify the need for tricuspid valve repair? J Am Coll Cardiol. 1989;14:1266–74.
Later work done with Nanda also used contrast injections in the cardiac catheterization laboratory to confirm the detection of pulmonary valve by echocardiography.18
In the 1970s, saline contrast was used for the delineation of intracardiac shunts for the identification of right-sided valves and for better assessment of congenital heart disease.18,7678 It was also used to identify and assess the severity of right-sided valvular regurgitation.79
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Fig. 1.18: Visualization of aortic stenosis (AS) jet. The right parasternal view shows a narrow band of mosaic signals (AS JET) originating from the thickened aortic valve during systole. The mosaic signals indicate the presence of turbulence. The jet is very narrow at its origin (jet width, 6 mm), implying severe aortic stenosis, but later broadens out to completely fill the ascending aorta (AA). (AV: Aortic valve; PA: Pulmonary artery).Source: Reproduced with permission from Fan P, Kapur KK, Nanda NC. Color-guided Doppler echocardiographic assessment of aortic valve stenosis. J Am Coll Cardiol. 1988;12:441–9.
13As recently as 2007, saline contrast was used by us for the first time to identify and validate the echo-free space behind the aorta, examined in the parasternal long-axis view, as the superior vena cava in most instances and only occasionally as the main or right pulmonary artery (Fig. 1.19).80 In the 1980s, commercial contrast agents with miniaturized stable microbubbles were developed. Gelatin-encapsulated nitrogen bubbles were shown to be stable for use with ultrasound enhancement,81 and microbubbles sonicated from human serum albumin were shown to traverse the pulmonary circulation and opacify the left ventricle.82 Some of the early work was pioneered by Drs. Sanjiv Kaul and Steve Feinstein. These observations led to the introduction of multiple contrast agents in the market with variable properties. The first agent approved by the Food and Drug Administration in the United States in 1994 utilized air as the gas component of the microbubbles, as did other agents at that time, which reduced the longevity of the bubbles.78 This is because air can leak out of the thin bubble shell and dissolve in the blood. In the 1990s, perfluorocarbon gases were utilized instead of air to increase the time these bubbles can persist in the circulation. These newer agents consisted of smaller and more stable microbubbles that proved to be helpful for the assessment of perfusion as well as enhancement and opacification and direct detection of coronary stenosis (Figs 1.20A and B).78,83,84 The first book to highlight advances in echo imaging using contrast enhancement was published in 1993.85
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Fig. 1.19: Validation of the structure behind the aorta as superior vena cava (SVC) by saline contrast echocardiography. Two-dimensional transthoracic echocardiographic bubble study. Intravenous injection of agitated normal saline shows contrast echoes first appearing in the bounded echo-free space (arrowhead) and then in the right ventricle (RV, arrow). This suggests that the echo-free space represents the SVC and not the main or right pulmonary artery. (AO: Aorta; LV: Left atrium; RV: Right ventricle).Source: Reproduced with permission from Burri MV, Mahan EF III, Nanda NC, Singh A, et al. Superior vena cava, right pulmonary artery or both: real time two- and three-dimensional transthoracic contrast echocardiographic identification of the echo free space posterior to the ascending aorta. Echocardiography. 2007;24:875–82.
 
TRANSESOPHAGEAL ECHOCARDIOGRAPHY
Transesophageal echocardiography was envisioned as early as 1971 by Side and Gosling for its use with Doppler,86 but it was first developed with M-mode by Frazin et al. in a classical article in Circulation in 1976.87 The use of this new technique was hampered because of its reliance on large rigid scopes. Hanrath was the first to attach a phased array transducer to the tip of a flexible scope, which ushered in the era of clinical transesophageal echocardiography.88 The technique found popularity because of the superior quality images obtained by the higher frequency probe used and the proximity of the esophagus to cardiac structures. Initially, a monoplane probe was used but subsequently biplane and multiplane probes were developed, and articles and books were published delineating the technique for systematic examination of cardiac structures.8991 It soon found wide application in the intraoperative setting in the cardiac catheterization laboratory during percutaneous procedures and in the echo laboratory as a valuable adjunct to 2D transthoracic echocardiography. It was found that during a transesophageal examination, important supplementary information could be provided by examining coronary arteries for stenosis and imaging the abdominal structures and vessels for abnormalities with the probe positioned in the stomach (transgastric ultrasonography; Figs 1.21 and 1.22).92,93 Toward the end of the examination with the probe positioned in the upper esophagus, one could evaluate the aortic arch branches and the adjacent veins in detail,9499 and also with the probe withdrawn into the pharynx, the carotid bulb on both sides, left and right internal carotid arteries, and extracranial segments of the vertebral arteries can be evaluated for stenosis and other abnormalities (transpharyngeal ultrasound; Figs 1.23A and B).100102 A distinct advantage of the transpharyngeal approach is the parallel orientation of the Doppler beam to the flow in the carotids, which is practically impossible to obtain with the usual external approach from the neck.
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Figs 1.20A and B: Transesophageal echocardiographic assessment of coronary arteries. Visualization and demonstration of stenosis by contrast echo enhancement. (A) Left panel: Linear flow signals (arrows) are demonstrated in the proximal left anterior descending coronary artery (LAD; without demonstrating the walls) following intravenous injection of Levovist, a contrast agent. Right panel: This LAD segment could not be demonstrated without contrast injection; (B) Left panel: Intravenous injection of Levovist not only demonstrated flow signals in the LAD but also showed an area of flow acceleration and aliasing corresponding to an area of severe stenosis in the proximal LAD on the coronary angiogram. Right panel: A smaller area of flow signals with a smaller flow acceleration persisting from a previous Levovist injection. Contrast enhancement is useful in demonstrating additional segments of the coronary arteries not visualized on routine examination and demonstrating stenoses in these segments.Source: Reproduced with permission from Agarwal KK, Gatewood RP, Nanda NC, et al. Improved transesophageal echocardiographic assessment of significant proximal narrowing of the left anterior descending and left circumflex coronary arteries using echo contrast enhancement. Am J Cardiol. 1994;73:1131–3.
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Fig. 1.21: Transesophageal echocardiographic assessment of coronary arteries. A long segment of the circumflex (CX) coronary artery is seen coursing laterally. (LA: Left atrium; LAD: Left anterior descending coronary artery; LM: Left main coronary artery).Source: Reproduced with permission from Nanda NC, Domanski MJ. Atlas of Transesophageal Echocardiography. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007: 31.
 
TISSUE DOPPLER AND SPECKLE TRACKING IMAGING
Since the velocity of blood is much faster than that of the cardiac tissue, usual Doppler imaging filters out slow-moving objects such as cardiac tissue in order to enhance the images. With tissue imaging, the reverse is done, whereby the fast velocities of the red blood cells are filtered out and the velocity of the tissue is captured. This principle was exploited early on in the history of echocardiography in order to image the velocity of the posterior wall as early as 1972.103 Development in tissue Doppler imaging in the 1990s allowed for imaging the velocity of myocardial motion and for the analysis of myocardial segments independently of each other.104,105 These improvements facilitated the use of tissue Doppler imaging in the assessment of left ventricular diastolic function and in the measurement of strain and strain-rate of the individual myocardial segments. Because of the limitations posed by the angle dependence of the Doppler beam, techniques based on real time, 2D echocardiography such as velocity vector imaging106 and speckle tracking imaging 107 were introduced a few years ago (Fig. 1.24).
 
THREE-DIMENSIONAL ECHOCARDIOGRAPHY
Since 2D echocardiography is not ideal for imaging 3D cardiac structures, several attempts were made over the years to develop 3D echocardiography.108114
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Figs 1.22A and B: Transgastric ultrasound for examination of abdominal structures and vessels. (A) Transgastric examination of the superior mesenteric and renal vessels. Transverse plane imaging. Both the superior mesenteric (SMA) and the left renal arteries (LRA) are visualized arising from the abdominal aorta (AO). The inset shows pulse wave (PW) Doppler velocity waveform obtained from the SMA. (SA: Splenic artery. (B) Schematic representation.Source: Reproduced with permission from Chouinard MD, Pinheiro L, Nanda NC, Sanyal RS. Transgastric ultrasonography: a new approach for imaging the abdominal structures and vessels. Echocardiography. 1991; 9:397–403.
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Figs 1.23A and B: Transpharyngeal ultrasound diagnosis of left carotid bulb and internal carotid artery stenosis. (A) Color Doppler examination demonstrating the ascending pharyngeal (AP) and other branches (arrows) of the left external carotid artery (LEC). The left internal jugular vein (LIJV) is seen adjacent to the left common carotid artery (LCC). (B) Color Doppler-guided pulsed and continuous-wave Doppler examination of the proximal left internal carotid (LIC) shows a peak systolic velocity of 1.8 m/s and a peak diastolic velocity approaching 1.0 m/s, indicative of significant stenosis. Note that the Doppler beam is aligned parallel to the flow direction in the proximal LIC.Source: Reproduced with permission from Nanda NC, Gomez, CR, Narayan VK, Tery JB, et al. Transpharyngeal echocardiographic diagnosis of carotid bulb and left internal carotid artery stenosis. Echocardiography. 1999;16:671–4.
Moritz and Shreve115 introduced the spark gap position-locating approach (an acoustic spatial locating system) to provide 3D coordinates, but this method was not capable of recording or viewing 3D images. The Nanda group113 used an approach that was able to image the left ventricle in three dimensions by placing a 2D transducer on a mechanical arm that allowed it to rotate around its axis. The transducer was rotated every few degrees in a sequential manner, and multiple slices of the heart at end systole and end diastole were obtained (Figs 1.25A and B). These were then reconstructed by a computer to obtain 3D images of the left ventricle. The volumes obtained using this method were validated by angiography. This work was further extended by the same group to successfully incorporate Doppler information and color Doppler reconstruction.116,117
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Fig. 1.24: Velocity vector imaging before and after cardiac resynchronization therapy. Velocity vector data obtained from the left ventricular short-axis view. The radial velocities in the lateral wall peak in late systole/early diastole prior to biventricular pacing. After biventricular pacing, the septal and lateral wall radial velocities are synchronous. Thus, cardiac resynchronization therapy (CRT) has improved radial myocardial contraction synchrony.Source: Reproduced with permission from Vannan MA, Pedrizzetti G, Lip P, Gurudevan S, Houle H, Main J, et al. Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging. Description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography. 2005;22;823–60.
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Figs 1.25A and B: (A) Three-dimensional reconstruction of transthoracic echocardiographic images by apical axis rotation method. The transducer rotation and different planes intersecting the heart are shown here. The transducer was held manually; (B) Subsequently, the transducer was mounted on a mechanical arm, which permitted only 1° of freedom—rotation about its axis.Source: Reproduced with permission from Ghosh A, Nanda NC, Maurer G. Three-dimensional reconstruction of echocardiographic images using the rotation method. Ultrasound Med Biol. 1982;8:655–61.
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Later, 3D transesophageal echocardiography was developed by mounting a monoplane probe on a sliding carriage within a casing. By moving the probe up and down the esophagus in small increments, transverse sections at various parallel cardiac levels were obtained and the images were then reconstructed using a computer to provide 3D images.118,119 This technique, developed by the TomTec Company (Munich, Germany), was limited due to the large size of the probe which precluded routine clinical use. The next step was to use a biplane transesophageal echocardiography probe for 3D imaging. In order to determine the probe rotation angle, a protractor mounted on the probe shaft guard was used. The probe was angulated at 90° and manually rotated in a clockwise direction in small increments to provide sequential longitudinal images that were then reconstructed in 3D using both B-mode and color Doppler (Fig. 1.26).120,121 Nanda et al122 then used a multiplane transesophageal echocardiography transducer to reconstruct 3D images by ensuring that the probe remained stationary at a given level and rotating it at 18° intervals at a time (Figs 1.27 and 1.28). Since with this technology the 3D dataset could be sliced in any direction similar to dissecting a piece of tissue, it allowed for the visualization of cardiac structures from any direction and the understanding of the complex relationship between structures. Several clinical applications ensued from this development (Figs 1.29A to C).123127
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Fig. 1.26: Three-dimensional reconstruction of transesophageal echocardiographic longitudinal images. Three-dimensional image of superior vena cava zone, showing three-dimensionally reconstructed longitudinal structures of superior vena cava (SVC), inferior vena cava (IVC), right atrium (RA), left atrium (LA), and right pulmonary artery (RPA).Source: Reproduced with permission from Li ZA, Wang XF, Nanda NC, et al. Three dimensional reconstruction of transesophageal echocardiographic longitudinal images. Echocardiography. 1995;12:367–75.
With 3D reconstruction imaging, imaging artifact was common because of the time needed for acquisition of images over several cardiac cycles with patient and/or probe motion during the procedure in addition to changes in heart rate. Live/real time, 3D imaging was thus developed and is currently the 3D technique used in clinical practice. Initial attempts at the development of 3D transthoracic echocardiography (TTE) resulted in a stand-alone system which was able to provide B-mode images only.128
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Fig. 1.27: Three-dimensional reconstruction of multiplane transesophageal echocardiographic images. Sequential multiplanar transesophageal two-dimensional images of the left ventricle were obtained by rotating the probe in small angular increments. These were then reconstructed to obtain a three-dimensional image of the left ventricle. (LA: Left atrium; LV: Left ventricle; RA: Right atrium; RV: Right ventricle).Source: Reproduced with permission from Nanda NC, Pinheiro L, Sanyal R, et al. Multiplane transesophageal echocardiographic imaging and three-dimensional reconstruction a preliminary study. Echocardiography. 1992;9:667–76.
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Fig. 1.28: Three-dimensional reconstruction of the left ventricle using sequential planes obtained from multiplane transesophageal examination in an adult patient. The “volume cast” of the left ventricular cavity is shown.Source: Reproduced with permission from Nanda NC, Pinheiro L, Sanyal R, et al. Multiplane transesophageal echocardiographic imaging and three-dimensional reconstruction a preliminary study. Echocardiography. 1992;9:667–76.
A matrix probe was then developed to provide live/real time, B-mode and color Doppler images, therefore, facilitating its use in day-to-day clinical practice.129 These datasets were obtained over four to eight cardiac beats. Further development resulted in real time, 3D imaging in which a dataset was obtained of an entire volume of the heart using only one or more cardiac cycles that could then be dissected along any direction.130 Another important innovation was the development of a single transducer to perform both 2D and live/real time, 3D studies. Subsequently, the transducer was incorporated in the transesophageal probe and live/real time, 3D transesophageal echocardiography was born. The first clinical study using this technology was published from the University of Alabama at Birmingham in 2007 (Fig. 1.30).131,132 This technique has found popularity in the operating room and cardiac catheterization laboratories for percutaneous procedures.
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Figs 1.29A and B: Three-dimensional transesophageal echocardiography. (A) Transesophageal three-dimensional reconstruction of the stenotic aortic valve. The aortic valve (AV) shows multiple echo-dense areas indicative of severe thickening and calcification. Although the AV is considerably distorted, three leaflets are easily identified in the systole. The aortic orifice is very small and measured 0.7 cm2 by planimetry; (B) Schematic diagram demonstrating that the maximum dimension of an object (in this case, a cylinder) can be obtained only if the ultrasound beam cuts through its longest dimension (true long axis) when using a multiplane probe. However, when the two-dimensional planes (dotted lines) are stacked together to obtain a three-dimensional image, the object (cylinder), including its long axis, can be viewed completely, even though it is not oriented parallel to the ultrasonic beam as it is rotated from 0° to 180°. As demonstrated here, it is not possible to image the true long axis of an intracardiac mass lesion or defect (such as an atrial septal defect) using multiplane two-dimensional transesophageal echocardiography unless it lies exactly parallel to the ultrasound beam as it is rotated from 0° to 180°. Therefore, the maximum size of a mass or defect may be underestimated by multiplane two-dimensional transesophageal echocardiography. On the other hand, with three-dimensional transesophageal reconstruction, multiple sequential two-dimensional images are stacked to reconstruct the entire object in three dimensions, permitting accurate assessment of all its dimensions. (LA: Left atrium; AV: Aortic valve area; RVO: Right ventricular outflow tract).Source: (A) Reproduced with permission from Nanda NC, Roychoudhury D, Chung SM, et al. Quantitative assessment of normal and stenotic aortic valve using transesophageal three-dimensional echocardiography. Echocardiography. 1994;11:617–25.Source: (B) Reproduced with permission from Nanda NC, Abd-El Rahman SM, Khatri G, et al. Incremental value of three-dimensional echocardiography over transesophageal multiplane two-dimensional echocardiography in qualitative and quantitative assessment of cardiac masses and defects. Echocardiography. 1995;12:619–28.
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Fig. 1.29C: Transesophageal three-dimensional echocardiographic examination of coronary arteries. There is a tight stenosis (arrow) of the circumflex coronary artery (LCX) imaged in long-axis view in three dimensions. The arrow points to an atrial branch. (AO: Aorta; LA: Left atrium; LMC: Left main coronary artery).Source: Reproduced with permission from Abd El-Rahman SM, Khatri G, Nanda N, et al. Transesophageal three-dimensional echocardiographic assessment of normal and stenosed coronary arteries. Echocardiography. 1996; 13:503–10.
 
PERSPECTIVE
The use of echocardiography over the last decades has changed the practice of cardiology. This modality has successfully evolved with the changing tides of time to continue to be relevant to practicing physicians. It started as a research tool with M-mode whose potential was limited to a handful of pathologies and a future that looked unpromising. Due to the work of multiple investigators with the vision to enhance this field, 2D echocardiography was developed, which helped clinicians in the evaluation of a wide array of diseases ranging from congenital and valvular heart disease to coronary artery disease. Further developments, including the introduction of conventional and color Doppler flow imaging, allowed for real time visualization of blood flow and opened the era of noninvasive hemodynamic cardiac assessment. With the introduction of 3D echocardiography, the dream of early pioneers of visualizing cardiac structures in a real-life perspective using ultrasound was realized. Echocardiography has become so useful to the clinician that it can be rightfully considered as an extension of clinical cardiac examination, more so because of the development of small, palm-sized handheld echocardiographic machines that can fit into the pocket of a white coat, like a stethoscope.133 We have not reached the end of the road. There is still room for improvement in the resolution of images as well as in the hardware and software used for the various applications. Education regarding the relevance of the newer ultrasound technologies to the cardiologist and echocardiographer is not optimal. Nevertheless, there is still reason to believe that echocardiography will continue to be the chief and most cost-effective cardiac imaging modality for decades to come.
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Fig. 1.30: Live/real time, three-dimensional transesophageal echocardiography. Mitral valve ring viewed en face by cropping from the atrial aspect. The arrow points to the en face view of the Duran ring.Source: Reproduced with permission from Pothineni KR, Inamdar V, Miller AP, Nanda NC, Bandarupalli N, Chaurasia P, et al. Initial experience with live/real time, three-dimensional transesophageal echocardiography. Echocardiography. 2007;24:1099–104.
REFERENCES
  1. Krishnamoorthy VK, Sengupta PP. Gentile F, et al. History of echocardiography and its future applications in medicine. Crit Care Med. 2007;35(8 Suppl):S309–13.
  1. Feigenbaum H. Evolution of echocardiography. Circulation. 1996;93(7):1321–7.

  1. 20 Pandian NG, Roelandt J, Nanda NC, et al. Dynamic three-dimensional echocardiography: methods and clinical potential. Echocardiography. 1994;11(3):237–59.
  1. Wade G. Human uses of ultrasound: ancient and modern. Ultrasonics. 2000;38(1-8):1–5.
  1. Edler I, Hertz CH. The use of ultrasonic reflectoscope for the continuous recording of the movements of heart walls. 1954. Clin Physiol Funct Imaging. 2004;24(3):118–36.
  1. Edler I, Lindström K. The history of echocardiography. Ultrasound Med Biol. 2004;30(12):1565–1644.
  1. Gowda RM, Khan IA, Vasavada BC, et al. History of the evolution of echocardiography. Int J Cardiol. 2004;97(1): 1–6.
  1. Edler I, Gustafson A. Ultrasonic cardiogram in mitral stenosis; preliminary communication. Acta Med Scand. 1957;159(2):85–90.
  1. Edler I. Ultrasound cardiography in mitral valve stenosis. Am J Cardiol. 1967;19(1):18–31.
  1. Edler I. Ultrasound cardiography. Ultrasonics. 1967;572–9.
  1. Edler I. Atrioventricular valve motility in the living human heart recorded by ultrasound. Acta Med Scand Suppl. 1961;37083–124.
  1. Edler I. The use of ultrasound as a diagnostic aid, and its effects on biological tissues. Continuous recording of the movements of various heart-structures using an ultrasound echo-method. Acta Med Scand Suppl. 1961;3707–65.
  1. Joyner CR Jr, Reid JM, Bond JP. Reflected ultrasound in the assessment of mitral valve disease. Circulation. 1963;27 (4 Pt 1):503–11.
  1. Feigenbaum H, Waldhausen JA, Hyde LP. Ultrasound diagnosis of pericardial effusion. JAMA. 1965;191711–14.
  1. Feigenbaum H, Popp RL, Wolfe SB, et al. Ultrasound measurements of the left ventricle. A correlative study with angiocardiography. Arch Intern Med. 1972;129(3):461–7.
  1. Pombo JF, Troy BL, Russell RO Jr. Left ventricular volumes and ejection fraction by echocardiography. Circulation. 1971;43(4):480–90.
  1. Popp RL, Harrison DC. Ultrasonic cardiac echography for determining stroke volume and valvular regurgitation. Circulation. 1970;41(3):493–502.
  1. Gramiak R, Nanda NC, Shah PM. Echocardiographic detection of the pulmonary valve. Radiology. 1972;102(1): 153–7.
  1. Gramiak R, Chung KJ, Nanda N, et al. Echocardiographic diagnosis of transposition of the great vessels. Radiology. 1973;106(1):187–9.
  1. Nanda NC, Gramiak R, Manning JA, et al. Echocardiographic features of subpulmonic obstruction in dextro-transposition of the great vessels. Circulation. 1975; 51(3):515–21.
  1. Nanda NC, Gramiak R, Robinson TI, et al. Echocardiographic evaluation of pulmonary hypertension. Circulation. 1974;50(3):575–81.
  1. Nanda NC, Gramiak R, Manning J, et al. Echocardiographic recognition of the congenital bicuspid aortic valve. Circulation. 1974;49(5): 870–5.
  1. Nanda NC, Steward S, Gramiak R, et al. Echocardiography of the intra-atrial baffle in dextro-transposition of the great vessels. Circulation. 1975;511130–5.
  1. Nanda NC, Gramiak R, Shah PM. Echocardiographic misdiagnosis of the severity of mitral stenosis. Clin Res. 1975;23199A.
  1. Feigenbaum H. Echocardiography. 1st ed. Lea & Febiger;,  Philadelphia,  PA: 1972.
  1. Nanda NC, Gramiak R. Clinical Echocardiography. C.V. Mosby;  St. Louis,  MO: 1978.
  1. Gramiak R, Waag RC, Simon W. Ciné ultrasound cardiography. Radiology. 1973;107(1):175–80.
  1. Bom N, Lancée CT, Honkoop J, et al. Ultrasonic viewer for cross-sectional analyses of moving cardiac structures. Biomed Eng. 1971;6(11):500–3, 5.
  1. Griffith JM, Henry WL. A sector scanner for real time two-dimensional echocardiography. Circulation. 1974;49(6): 1147–52.
  1. Reeves WC, Nanda NC, Barold SS. Echocardiographic evaluation of intracardiac pacing catheters: M-mode and two-dimensional studies. Circulation. 1978;58(6):1049–56.
  1. Gondi B, Nanda NC. Real-time, two-dimensional echocardiographic features of pacemaker perforation. Circulation. 1981;64(1):97–106.
  1. Harris JP, Nanda NC, Moxley R, et al. Myocardial perforation due to temporary transvenous pacing catheters in pediatric patients. Cathet Cardiovasc Diagn. 1984;10(4):329–33.
  1. Schuster AH, Zugibe F Jr, Nanda NC, et al. Two-dimensional echocardiographic identification of pacing catheter-induced thrombosis. Pacing Clin Electrophysiol. 1982;5(1):124–8.
  1. Rosenbloom M, Saksena S, Nanda NC, et al. Two-dimensional echocardiographic studies during sustained ventricular tachycardia. Pacing Clin Electrophysiol. 1984; 7(1):136–42.
  1. Gatewood RP Jr, Nanda NC. Differentiation of left ventricular pseudoaneurysm from true aneurysm with two dimensional echocardiography. Am J Cardiol. 1980;46(5):869–78.
  1. Gondi B, Nanda NC. Two-dimensional echocardiographic features of atrial septal aneurysms. Circulation. 1981;63(2): 452–7.
  1. D'Arcy BJ, Nanda NC. Two-dimensional echo features of right ventricular infarction. Circulation. 1982;65167–73.
  1. Bhandari AK, Nanda NC. Two-dimensional echocardiographic recognition of abnormal changes in the myocardium. Ultrasound Med Biol. 1982;8(6):663–71.
  1. Bhandari AK, Nanda NC, Hicks DG. Two-dimensional echocardiography of intracardiac masses: echo pattern-histopathology correlation. Ultrasound Med Biol. 1982;8(6): 673–80.
  1. Maurer G, Nanda NC. Two dimensional echocardiographic evaluation of exercise-induced left and right ventricular asynergy: correlation with thallium scanning. Am J Cardiol. 1981;48(4):720–7.
  1. Oberman A, Fan PH, Nanda NC, et al. Reproducibility of two-dimensional exercise echocardiography. J Am Coll Cardiol. 1989;14(4):923–8.
  1. Gondi B, Nanda NC. Cold pressor test during real time two-dimensional echocardiography: usefulness in detection of patients with coronary artery disease. Am Heart J. 1984;107: 278–85.

  1. 21 Mathew T, Nanda NC. Two-dimensional and Doppler echocardiographic evaluation of aortic aneurysm and dissection. Am J Cardiol. 1984;54(3):379–85.
  1. Baran A, Nanda NC, Falkoff M, et al. Two-dimensional echocardiographic detection of arrhythmogenic right ventricular dysplasia. Am Heart J. 1982;103(6):1066–7.
  1. TInker DD, Nanda NC, Harris JP, et al. Two-dimensional echocardiographic identification of pulmonary artery branch stenosis. Am J Cardiol. 1982;50(4):814–20.
  1. Bhandari AK, Nanda NC. Pulmonary artery aneurysms: echocardiographic features in 5 patients. Am J Cardiol. 1984;53(10):1438–41.
  1. Reinold E. [”On the colored light of double stars and certain other stars of heaven” and what happened hence]. Ultraschall Med. 2004;25(2):101–4.
  1. Satomura S. A study on examining the heart with ultrasonics. I. Principles; II. Instrument. Jpn Circ J. 1956;20227–8.
  1. Rushmer RF, Baker DW, Stegall HF. Transcutaneous Doppler flow detection as a nondestructive technique. J Appl Physiol. 1966;21(2):554–66.
  1. Baker DW, Rubenstein SA, Lorch GS. Pulsed Doppler echocardiography: principles and applications. Am J Med. 1977;63(1):69–80.
  1. Holen J, Simonsen S. Determination of pressure gradient in mitral stenosis with Doppler echocardiography. Br Heart J. 1979;41(5):529–35.
  1. Hatle L, Angelsen BA, Tromsdal A. Non-invasive assessment of aortic stenosis by Doppler ultrasound. Br Heart J. 1980;43(3):284–92.
  1. Hatle L, Brubakk A, Tromsdal A, et al. Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. Br Heart J. 1978;40(2):131–40.
  1. Nanda NC, Hodsden J, Santelli S. Pulse Doppler echocardiography of coronary arteries: methodology and clinical usefulness. Am J Cardiol. 1982;49:932.
  1. Maulik D, Saini VD, Nanda NC, et al. Doppler evaluation of fetal hemodynamics. Ultrasound Med Biol. 1982;8(6): 705–10.
  1. Maulik D, Nanda NC, Saini VD. Fetal Doppler echocardiography: methods and characterization of normal and abnormal hemodynamics. Am J Cardiol. 1984;53(4):572–8.
  1. Hatle L, Angelsen B. Doppler Ultrasound in Cardiology—Physical Principles and Clinical Applications. Lea & Febiger;  Philadelphia,  PA: 1982.
  1. Nanda NC, editor. Doppler Echocardiography. Igaku-Shoin Medical Publishers;  New York:  1985.
  1. Zugibe FT Jr, Nanda NC, Barold SS, et al. Usefulness of Doppler echocardiography in cardiac pacing: assessment of mitral regurgitation, peak aortic flow velocity and atrial capture. Pacing Clin Electrophysiol. 1983;6(6):1350–7.
  1. Nanda NC, Bhandari A, Barold SS, et al. Doppler echocardiographic studies in sequential atrioventricular pacing. Pacing Clin Electrophysiol. 1983;6(4):811–14.
  1. Omoto R, Yokote Y, Takamoto S, et al. The development of real-time two-dimensional Doppler echocardiography and its clinical significance in acquired valvular diseases. With special reference to the evaluation of valvular regurgitation. Jpn Heart J. 1984;25(3):325–40.
  1. Kasi C, Namekawa K, Koyano A, et al. Real-time two-dimensional blood flow imaging using an autocorrelation technique. IEEE Trans Sonics Ultrason. 1985;SU-32;458–64.
  1. Helmcke F, Nanda NC, Hsiung MC, et al. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation. 1987;75(1):175–83.
  1. Perry GJ, Helmcke F, Nanda NC, et al. Evaluation of aortic insufficiency by Doppler color flow mapping. J Am Coll Cardiol. 1987;9(4):952–9.
  1. Chopra HK, Nanda NC, Fan P, et al. Can two-dimensional echocardiography and Doppler color flow mapping identify the need for tricuspid valve repair? J Am Coll Cardiol. 1989;14(5):1266–74.
  1. Dagli SV, Nanda NC, Roitman D, et al. Evaluation of aortic dissection by Doppler color flow mapping. Am J Cardiol. 1985;56(7):497–8.
  1. Fan PH, Kapur KK, Nanda NC. Color Doppler assessment of aortic valve stenosis. J Am Coll Cardiol 1988;12441–9.
  1. Kapur KK, Fan P, Nanda NC, et al. Doppler color flow mapping in the evaluation of prosthetic mitral and aortic valve function. J Am Coll Cardiol. 1989; 13(7):1561–71.
  1. Maulik D, Nanda NC, Hsiung MC, et al. Doppler color flow mapping of the fetal heart. Angiology. 1986;37(9):628–32.
  1. Zachariah ZP, Hsiung MC, Nanda NC, et al. Color Doppler assessment of mitral regurgitation induced by supine exercise in ischemic heart disease. Am J Cardiol. 1987;59: 1266–70.
  1. Jain S, Pinheiro L, Nanda NC, et al. Noninvasive assessment of renal artery stenosis by combined conventional and color Doppler ultrasound. Echocardiography. 1990;7(6): 679–88.
  1. Omoto R, editor. Color Atlas of Real-Time Two-Dimensional Doppler Echocardiography. Shindan-To-Chiryo Col;t  Tokyo,  Japan: 1984.
  1. Nanda NC. Atlas of Color Doppler Echocardiography. Lea & Febiger;  Philadelphia,  PA: 1989.
  1. Nanda NC, editor. Textbook of Color Doppler Echocardiography. Lea & Febiger;  Philadelphia,  PA: 1989.
  1. Gramiak R, Shah PM. Echocardiography of the aortic root. Invest Radiol. 1968;3(5):356–66.
  1. Rothbard RL, Nanda NC. Contrast echocardiography. Semin Ultrasound. 1981;2167–72.
  1. Nanda NC, Gramiak R, Manning JA. Echocardiography of the tricuspid valve in congenital left ventricular-right atrial communication. Circulation. 1975;51(2):268–72.
  1. Miller AP, Nanda NC. Contrast echocardiography: new agents. Ultrasound Med Biol. 2004;30(4):425–34.
  1. Nanda NC, Shah PM, Gramiak R. Echocardiographic evaluation of tricuspid valve incompetence by contrast injections. Clin Res. 1976;24233A.
  1. Burri MV, Mahan EF 3rd, Nanda NC, et al. Superior vena cava, right pulmonary artery or both: real time two- and three-dimensional transthoracic contrast echocardiographic identification of the echo-free space posterior to the ascending aorta. Echocardiography. 2007;24(8):875–82.
  1. Carroll BA, Turner RJ, Tickner EG, et al. Gelatin encapsulated nitrogen microbubbles as ultrasonic contrast agents. Invest Radiol. 1980;15(3):260–6.

  1. 22 Feinstein SB, Shah PM, Bing RJ, et al. Microbubble dynamics visualized in the intact capillary circulation. J Am Coll Cardiol. 1984;4(3):595–600.
  1. Nanda NC, Wistran DC, Karlsberg RP, et al. Multicenter evaluation of SonoVue for improved endocardial border delineation. Echocardiography. 2002;19(1):27–36.
  1. Nanda NC, Kitzman DW, Dittrich HC, et al. Imagent Clinical Investigators Group. Imagent improves endocardial border delineation, inter-reader agreement, and the accuracy of segmental wall motion assessment. Echocardiography. 2003;20(2):151–61.
  1. Nanda NC, Schlief R, editors. Advances in Echo Imaging Using Contrast Enhancement. Kluwer Academic Publishers;  Dordrecht,  The Netherlands: 1993.
  1. Side CD, Gosling RG. Non-surgical assessment of cardiac function. Nature. 1971;232(5309):335–6.
  1. Frazin L, Talano JV, Stephanides L, et al. Esophageal echocardiography. Circulation. 1976;54(1):102–8.
  1. Hanrath P, Kremer P, Langenstein BA, et al. [Transesophageal echocardiography. A new method for dynamic ventricle function analysis]. Dtsch Med Wochenschr. 1981; 106(17):523–5.
  1. Seward JB, Khandheria BK, Oh JK, et al. Transesophageal echocardiography: technique, anatomic correlations, implementation, and clinical applications. Mayo Clin Proc. 1988;63(7):649–80.
  1. Nanda NC, Pinheiro L, Sanyal RS, et al. Transesophageal biplane echocardiographic imaging: technique, planes, and clinical usefulness. Echocardiography. 1990;7(6):771–88.
  1. Nanda NC, Domanski M. Atlas of Transesophageal Echocardiography. Williams & Wilkins;  Baltimore,  MD: 1998.
  1. Samdarshi TE, Nanda NC, Gatewood RP Jr, et al. Usefulness and limitations of transesophageal echocardiography in the assessment of proximal coronary artery stenosis. J Am Coll Cardiol. 1992;19(3):572–80.
  1. Chouinard MD, Pinheiro L, Nanda NC, et al. Transgastric ultrasonography: a new approach for imaging the abdominal structures and vessels. Echocardiography. 1991;8 397–403.
  1. Agrawal G, LaMotte LC, Nanda NC, et al. Identification of the Aortic Arch Branches Using Transesophageal Echocardiography. Echocardiography. 1997;14(5):461–6.
  1. LaMotte LC, Nanda NC, Thakur AC, et al. Transesophageal Echocardiographic Identification of Neck Veins: Value of Contrast Echocardiography. Echocardiography. 1998;15(3): 259–68.
  1. Nanda NC, Biederman RW, Thakur AC, et al. Examination of Left External and Internal Carotid Arteries During Transesophageal Echocardiography. Echocardiography. 1998;15(8 Pt 1):755–8.
  1. Nanda NC, Thakur AC, Thakur D, et al. Transesophageal Echocardiographic Examination of Left Subclavian Artery Branches. Echocardiography. 1999;16(3):271–7.
  1. Nanda NC, Nekkanti R, Melendez A, et al. Transesophageal two-dimensional echocardiographic demonstration of the innominate artery and its branches. Am J Geriatr Cardiol. 2001;10(6):368–70.
  1. Aaluri S, Miller AP, Nanda NC, et al. Transesophageal echocardiographic detection of left vertebral artery origin stenosis. Echocardiography. 2002;19(8):695–7.
  1. Nanda NC, Gomez CR, Narayan VK, et al. Transpharyngeal Echocardiographic Diagnosis of Carotid Bulb and Left Internal Carotid Artery Stenosis. Echocardiography. 1999; 16(7, Pt 1):671–4.
  1. Miller A, Nanda NC, Mukhtar O, et al. Transpharyngeal echocardiographic detection of a left internal carotid artery stent. Echocardiography. 2000;17(8): 739–41.
  1. Khanna D, Cheng PH, Nanda NC, et al. Transpharyngeal ultrasound detection of carotid body paraganglioma. Echocardiography. 2004;21(3):299–301.
  1. Kostis JB, Mavrogeorgis E, Slater A, et al. Use of a range-gated, pulsed ultrasonic Doppler technique for continuous measurement of velocity of the posterior heart wall. Chest. 1972;62(5):597–604.
  1. McDicken WN, Sutherland GR, Moran CM, et al. Colour Doppler velocity imaging of the myocardium. Ultrasound Med Biol. 1992;18(6-7):651–4.
  1. Miyatake K, Yamagishi M, Tanaka N, et al. New method for evaluating left ventricular wall motion by color-coded tissue Doppler imaging: in vitro and in vivo studies. J Am Coll Cardiol. 1995;25(3):717–24.
  1. Vannan MA, Pedrizzetti G, Li P, et al. Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging: description and initial clinical application of a novel method using high-frame rate B-mode echocardiographic images. Echocardiography. 2005;22(10):826–30.
  1. Geyer H, Caracciolo G, Abe H, et al. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010;23(4):351–69; quiz 453.
  1. Dekker DL, Piziali RL, Dong E Jr. A system for ultrasonically imaging the human heart in three dimensions. Comput Biomed Res. 1974;7(6):544–53.
  1. Geiser EA, Lupkiewicz SM, Christie LG, et al. A framework for three-dimensional time-varying reconstruction of the human left ventricle: sources of error and estimation of their magnitude. Comput Biomed Res. 1980;13(3):225–41.
  1. King D, Al-Bana S, Larach D. A new three-dimensional random scanner for ultrasonic/computer graphic imaging of the heart. In: White DN, Barnes R, editors. Ultrasound in Medicine.  New York;  1975: 363–72.
  1. Moritz WE, Pearlman AS, McCabe DH, et al. An ultrasonic technique for imaging the ventricle in three dimensions and calculating its volume. IEEE Trans Biomed Eng. 1983;30(8):482–92.
  1. Matsumoto M, Matsuo H, Kitabatake A, et al. Three-dimensional echocardiograms and two-dimensional echocardiographic images at desired planes by a computerized system. Ultrasound Med Biol. 1977;3(2-3):163–78.
  1. Ghosh A, Nanda NC, Maurer G. Three-dimensional reconstruction of echo-cardiographic images using the rotation method. Ultrasound Med Biol. 1982;8(6):655–61.

  1. 23 Handschumacher MD, Lethor JP, Siu SC, et al. A new integrated system for three-dimensional echocardiographic reconstruction: development and validation for ventricular volume with application in human subjects. J Am Coll Cardiol. 1993;21(3):743–53.
  1. Moritz WE, Shreve PL. A microprocessor based spatial locating system for use with diagnostic ultrasound. Proc IEEE. 1976;64966–74.
  1. Raqueno R, Ghosh A, Nanda NC. Four-dimensional reconstruction of two-dimensional echocardiographic images. Echocardiography. 1989;6323–37.
  1. Schott JR, Raqueno R, Ghosh A, et al. Four dimensional cardiac blood flow analysis using color Doppler echocardiography. In: Nanda NC, editor. Textbook of Color Doppler Echocardiography. Lea & Febiger;  Philadelphia,  PA: 1989: 332–41.
  1. Wollschlager H, Zeiher AM, Klein H, et al. Transesophageal echo computer tomography: a new method for dynamic 3-D imaging of the heart (Echo-CT). Comp Cardiol IEEE Comp Soc. 1990;39.
  1. Pandian NG, Nanda NC, Schwartz SL, et al. Three-dimensional and four-dimensional transesophageal echocardiographic imaging of the heart and aorta in humans using a computed tomographic imaging probe. Echocardiography. 1992;9(6):677–87.
  1. Li ZA, Wang XF, Nanda NC, et al. Three dimensional reconstruction of transesophageal echocardiographic longitudinal images. Echocardiography. 1995;12367–75.
  1. Li Z, Wang X, Xie M, Nanda NC, Hsiung MC. Dynamic Three-Dimensional Reconstruction of Abnormal Intracardiac Blood Flow. Echocardiography. 1997;14(4):375–82.
  1. Nanda NC, Pinheiro L, Sanyal R, et al. Multiplane transesophageal echocardiographic imaging and three-dimensional reconstruction. Echocardiography. 1992;9 667–76.
  1. Nanda NC, Abd El-Rahman SM, Khatri GK, et al. Incremental value of three-dimensional echocardiography over transesophageal multiplane two-dimensional echocardiography in qualitative and quantitative assessment of cardiac masses and defects. Echocardiography. 1995;12(6):619–28.
  1. Nanda NC, Roychoudhury D, Chung SM, et al. Quantitative assessment of normal and stenotic aortic valve using transesophageal three-dimensional echocardiography. Echocardiography. 1994;11(6):617–25.
  1. Abd El-Rahman SM, Khatri G, Nanda NC, et al. Transesophageal three-dimensional echocardiographic assessment of normal and stenosed coronary arteries. Echocardiography. 1996;13503–10.
  1. Nanda NC, Khatri GK, Samal AK, et al. Three-Dimensional Echocardiographic Assessment of Aortic Dissection. Echocardiography. 1998;15(8 Pt 1):745–54.
  1. Nanda NC, Sorrell VL, editors. Atlas of Three-Dimensional Echocardiography. Futura;  Armonk,  NY: 2002.
  1. Sheikh K, Smith SW, von Ramm O, et al. Real-time, three-dimensional echocardiography: feasibility and initial use. Echocardiography. 1991;8(1):119–25.
  1. Salgo I, Bianchi M. Going “live” with 3-D cardiac ultrasound. Today Cardiol. 2002;5.
  1. Hage FG, Nanda NC. Real-time three-dimensional echocardiography: a current view of what echocardiography can provide? Indian Heart J. 2009;61(2):146–55.
  1. Pothineni KR, Inamdar V, Miller AP, et al. Initial experience with live/real time three-dimensional transesophageal echocardiography. Echocardiography. 2007;24(10): 1099–104.
  1. Nanda NC, Hsiung MC, Miller AP, et al. Live/Real Time 3D Echocardiography. Wiley-Blackwell;  Oxford,  UK: 2010.
  1. Mondillo S, Giannotti G, Innelli P, et al. Hand-held echocardiography: its use and usefulness. Int J Cardiol. 2006;1111–5.