# **FOUR DIMENSIONAL FETAL ECHOCARDIOGRAPHY**

# **EDITORS**

Giuseppe Rizzo, MD Department of Obstetrics and Gynecology Università Roma Tor Vergata Rome Italy

Domenico Arduini, MD Department of Obstetrics and Gynecology Università Roma Tor Vergata Rome Italy

© 2010 by the Editor / Authors. Chapters in this eBook are Open Access and distributed under the Creative Commons Attribution (CC BY 4.0) license, which allows users to download, copy and build upon published chapters, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book taken as a whole is © 2010 Bentham Science Publishers under the terms and conditions of the Creative Commons license CC BY-NC-ND.

# **CONTENTS**

# **FOREWORD**

When Drs Rizzo and Arduini asked me to write this preface, I was honored and thrilled to have the opportunity to introduce this outstanding work!

Examining the fetal heart has always presented a huge challenge for ultrasound specialists. When I started in ultrasound 30 years ago, no one knew how to perform or even attempt the examination of the heart. Fetal echocardiography has progressed very rapidly, fueled by advances in image quality as well as increasing focus of the ultrasound community on the need for a proper examination of the heart. Even today, the detection of congenital heart defects remains at the very bottom of the list of identifiable abnormalities on a standard fetal sonogram, and well under 50% of congenital heart defects are identified by prenatally. Detection of congenital heart disease has lagged behind the successful detection of other abnormalities of the fetus despite our best attempts to teach the necessary skills. The fetal heart is a difficult organ to evaluate due its very small size, complex anatomy, dynamic blood flow physiology, as well as rapid rhythmical movement.

The importance of evaluating the heart cannot be over emphasized. Heart defects are among the most common malformations in the developing fetus and many of these anomalies are part of complex syndromes such as aneuploidies. Heart anomalies that occur as isolated defects are among the most challenging to detect, but are particularly important due to the need to prepare for a potentially sick newborn at delivery. I remember back in the early 80's when I first started in fetal ultrasound, the heart remained an enigma for many years and it was only after I missed several congenital heart defects in a row that I took on the enormous task of understanding the fetal heart and how it works. Unfortunately back then we did not have any books or educational aids such as Drs Rizzo and Arduini's wonderful e-book to guide us in learning how to evaluate the fetal heart.

I have been impressed for many years with the careers of Dr. Rizzo and Dr. Arduini who have made enormous contributions in the field of fetal imaging and in particular fetal echocardiography. They have both published extensively on this subject and are extremely well qualified to write and edit such a book. Drs Rizzo and Arduini have made significant contributions in fetal echocardiography over many years and have been instrumental in developing many of the Doppler aspects of the fetal heart evaluation. They have assembled an impressive group of authors here, and have edited a first class book on 3-D and 4-D of the fetal heart. They have understood that 3-D and 4-D volume imaging are necessary to evaluate the fetal heart due to its inherent complexity of motion, flow and anatomy.

The book is very well organized in multiple short chapters that are beautifully illustrated both with ultrasound images and diagrams. Initially, they introduce the subject with a chapter on the epidemiology of fetal heart defects and why they are important. Next are the basic chapters on screening and on normal anatomy, which are key for the beginners as well as the more seasoned examiner. The following chapters introduce 3-D and 4D ultrasound, starting with technical aspects of how to obtain a good image. Many practitioners are intimidated by the complexity of obtaining 3-D and 4-D images. The chapters that introduce the technical aspects of 3-D such as image display and manipulation of the image are all superb introductions on how to produce the best image. The book then focuses on 3-D and 4-D evaluation of blood flow using Doppler, a key subject in the evaluation of the heart. Additional chapters cover new technologies, such as the use of the matrix probe and the automated screening possibilities for the fetal heart. This volume includes the often forgotten venous anatomy of the heart and its connections, an extraordinarily valuable chapter. The chapters on anomalies are divided into septal defects, right heart, left heart, and cono truncal abnormalities and each chapter combines 2-D, 3-D/4-D and Doppler in the demonstration of these malformations. The book also describes the state of the art for 1st trimester echocardiography, followed by quantitative aspects of the function of the fetal heart including stroke volume and cardiac output. The last chapter involves other forms of imaging of the fetal heart, such as, MRI.

This book, while very comprehensive, remains simple in its approach. It makes a very complex and rather intimidating organ accessible to both the novice and the seasoned examiner. Furthermore, this book is presented as an E book which is a very innovative format, awaited with great anticipation. Such novel media will challenge the primacy of bulky printed books. Many books will soon be available as E books and carried as a small discrete thumb-drive or even down loaded perhaps on an electronic device such as a Kindle. Electronic versions of books are **ii**

the future of our industry and Drs. Rizzo and Arduini have stepped up to the plate in choosing such a modern and practical display for their book.

In conclusion, I am very excited about this E book, not only because of its superbly organized, well illustrated and presented content, but also because as an E book it can be carried and propagated throughout our community much more easily than a hard copy book would be. The authors have succeeded admirably in their endeavor to produce what promises to be a outstanding resource on the examination of the fetal heart.

**Beryl R. Benacerraf M.D.**

Clinical Professor of OB GYN and Radiology Harvard Medical School Boston Massachusetts

# **PREFACE**

The examination of the fetal heart is part of the comprehensive fetal scan, but this examination is still considered a challenge even for experienced sonographers. Over the years the number of ultrasound techniques used in fetal cardiology impressively increased and no other fetal organ is examined with as many modalities as the fetal heart including high resolution two dimensional (2D) imaging, M-mode examination, spectral, color, power, highdefinition digital Doppler, B flow as well as tissue Doppler. It is, however, common knowledge that despite the availability of all these technologies, screening programs, especially when limited to the study of the "four chamber view", have shown disappointing low detection rates for congenital heart disease (CHD). Although the identification of CHD can be improved by routinely visualizing the outflow tracts, their diagnosis is greatly affected by the skill of the operator as well as his ability to interpret the findings.

Very recently three- and four- dimensional (3D and 4D) technologies have been introduced in fetal cardiology and have revolutionized the way in which it is possible to study the heart. 4D ultrasonography may reduce the operator dependency of CHD diagnosis and adds the possibility to obtain offline virtual planes in cardiac examinations, views of the fetal heart difficult or impossible to obtain with conventional 2D ultrasound.

This new fetal cardiology ebook, we believe, will be of great value for all practicing clinicians wanting to start the study of the fetal heart with 4D ultrasonography. We have chosen a panel of contributors that are both leaders in this field and can represent the differences in practice between Europe and United States This is a comprehensive guide intended for anyone interested in fetal heart scanning performing both routine screening ultrasonographic examinations and targeted heart scans. It aims to assist the reader with the following questions: how can I use this technology to acquire cardiac volumes?, how do I handle cardiac volume data sets after acquisition? , how can I improve diagnosis and definition of CHD?

It is our hope that this book will provide a bridge between scientists using and testing new technologies for research purposes and clinicians wishing to improve their daily practice.

**Domenico Arduini Giuseppe Rizzo**

# **CONTRIBUTORS**

**Alfred Abuhamad, MD**  Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA

#### **Reuven Achiron, MD**

Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

#### **Domenico Arduini, MD**

Department of Obstetrics and Gynecology Università Roma Tor Vergata Rome Italy

#### **Timothy Bennett, MD**

Department of Obstetrics and Gynecology, University of Missouri-Kansas City School Medicine, Kansas City, MI, USA

### **Gianluca Campobasso, MD**  Fetal Medicine Unit,

Di Venere and Sarcone Hospitals. ASL Bari. Bari, Italy

**Rabih Chaoui,MD**  Prenatal Diagnosis and Human Genetics Berlin, Germany

#### **Sarah M Cohen, MD**

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Centers – Mt. Scopus, Jerusalem, Israel

## **Valentina De Robertis, MD**

Fetal Medicine Unit, Di Venere and Sarcone Hospitals. ASL Bari. Bari, Italy

# **Greggory R. De Vore, MD**  Fetal Diagnostic Center Pasadena, CA USA

**Marco Di Maurizio, MD**  Department of Radiology, Ospedale Meyer Florence, Italy

# **Jimmy Espinoza, MD**

Department of Obstetrics and Gynecology William Beaumont Hospital Royal Oak, MI USA

#### **Giuliano Farina, PhD**

Department of Obstetrics and Gynecology Azienda Ospedaliera "C.Poma" Mantova, Italy

#### **Laura Franceschetti, MD**

Department of Obstetrics and Gynecology Azienda Ospedaliera "C.Poma" Mantova , Italy

#### **Michal Lipscheutz, MD**

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Centers – Mt. Scopus, Jerusalem, Israel

#### **Pietro Gaglioti, MD**

Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, University of Turin, Turin Italy

#### **Liat Gindes, MD**

Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

#### **Gianpaolo Grisolia, MD**

Department of Obstetrics and Gynecology Azienda Ospedaliera "C.Poma" Mantova, Italy

### **Maurice Guirgis, MD**

University Paris VII Service Explorations Fonctionnelles Hôpital Robert Debré Paris France

#### **Wesley Lee, MD**

Division of Fetal Imaging, William Beaumont Hopsital, Royal Oak, MI, USA

### **Lucia Manganaro, MD,**

Department of Radiology, Università "La Sapienza" Rome, Italy

#### **Dev Maulik, MD, PhD,**

Department of Obstetrics and Gynecology, University of Missouri-Kansas City School Medicine, Kansas City, Missouri, USA

**Baruch Messing, MD**  Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Centers – Mt. Scopus, Jerusalem, Israel

# **David Mundy, MD,**  Department of Obstetrics and Gynecology, University of Missouri-Kansas City School Medicine, Kansas City, Missouri, USA

# **Roberta Iacobelli, MD**  Department of Pediatric Cardiology and Cardiac Surgery Bambino Gesu' Hospital, Rome Italy

## **Manuela Oberto, MD**

Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, University of Turin, Turin Italy

## **Giovanna Oggè, MD**

Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, University of Turin, Turin Italy

#### **Dario Paladini, MD**

Fetal Medicine & Cardiology Unit, Department of Obstetrics and Gynecology, University Federico II of Naples Naples, Italy

#### **Luciano Pasquini, MD**

Department of Pediatric Cardiology and Cardiac Surgery Bambino Gesu' Hospital, Rome Italy

# **Georgios Rembouskos, MD**

Fetal Medicine Unit, Di Venere and Sarcone Hospitals. ASL Bari. Bari, Italy

#### **Giuseppe Rizzo, MD**

Department of Obstetrics and Gynecology Università Roma Tor Vergata Rome Italy

#### **Roberto Romero, MD**

Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS, Hutzel Women's Hospital Detroit, MI, USA

#### **vi**

**Sara Savelli, MD**  Department of Radiology, Università "La Sapienza" Rome, Italy

**Gabriella Sglavo, MD**  Fetal Medicine & Cardiology Unit, Department of Obstetrics and Gynecology, University Federico II of Naples Naples, Italy

# **Elena Sinkovskaya, MD**  Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA USA

**Fabrizio Taddei**; **MD**  Department of Obstetrics and Gynecology Azienda Ospedaliera "C.Poma" – Mantova - Italy

**Tullia Todros, MD**  Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, University of Turin, Turin Italy

**Alessandra Toscano, MD**  Department of Pediatric Cardiology and Cardiac Surgery Bambino Gesu' Hospital, Rome Italy

# **Dan V Valsky, MD**

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Centers – Mt. Scopus, Jerusalem, Israel

#### **Nicola Volpe, MD**

Fetal Medicine Unit, Di Venere and Sarcone Hospitals. ASL Bari. Bari, Italy

### **Paolo Volpe, MD**

Fetal Medicine Unit, Di Venere and Sarcone Hospitals. ASL Bari. Bari, Italy

**Alina Weissmann-Brenne,MD**

Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

# **Simcha Yagel, MD**

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Centers – Mt. Scopus, Jerusalem, Israel

## **Lami Yeo, MD**

Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Perinatology Research Branch Intramural Division, NICHD, NIH, DHHS, Hutzel Women's Hospital Detroit, MI, USA

# **CHAPTER 1**

# **Epidemiology of Congenital Heart Diseases**

# **Maurice Guirgis\***

*Service Explorations Fonctionnelles Hôspital Robert Debré PARIS- FRANCE*

**Abstract**: Congenital heart defects (CHD) are among the most common birth defects, occurring in 5 to 10 per 100 live births. This substantial variation in the reported epidemiology of CHD is due to differences in applied methodologies. An increasing total prevalence of CHD has been recently reported, mainly due to increase in prevalence of small defects easily diagnosed by echocardiography, as well as an increase in prevalence of conotruncal defects and atrioventricular septal defects.In order to provide a comprehensive epidemiological overview, future studies should use international classification system as well as consistent inclusion and exclusion criteria. Futher studies are also required to evaluate precisely the impact of fetal cardiac diagnosis on the prevalence and outcome of CHD. Epidemiology of CHD provides an overview of the distribution and characteristics of risk factors. Environmental potential risk factors are reviewed as they may provide an opportunity for prevention of some forms of CHD.

**Key Words**: Congenital Heart Disease, Epidemiology, Environmental Risk Factor.

#### **INTRODUCTION**

Congenital heart defects (CHD) defined as "gross structural anomalies of the heart or intrathoracic vessels that are actually or potentially of functional significance", are among the most common congenital anomalies affecting about 5 to 10 per 1000 live births and are considered as the leading cause of infant deaths resulting from congenital anomalies [1,2,3].

#### **CAVEATS IN ASSESSMENT OF INCIDENCE OF CHD**

Accurate determination of the incidence of CHD is difficult and subject to great variation across different populations and registries: some mild and asymptomatic cases may not be diagnosed and consequently they are underestimated; other severe cases may die in the neonatal period without a diagnosis or autopsy done. However development of echocardiography as an accurate diagnostic tool for CHD [2], resulted in increased estimated values for incidence of CHD, secondary to improved prenatal diagnosis [4,5], as well as improved diagnosis of overlooked and mild lesions (e.g., increased diagnosis of cases with small atrial septal defects (ASD), and isolated small ventricular septal defects (VSD), which tend to resolve spontaneously).

To avoid confusion, and in order to provide a comprehensive review, epidemiological studies reporting total prevalence of CHD, should cover a geographically well defined area, and should include CHD occurring in live births, termination of pregnancy, late miscarriages and stillbirths. Cases with functional or unspecified cardiac murmur, patent ductus arteriosus (PDA) associated to prematurity, peripheral pulmonary artery stenosis (PPS), should be excluded, according to the European Surveillance of congenital anomalies EUROCAT exclusion list [6]. Furthermore, it is better to relate the absolute incidence of each specific lesion, to live births, rather than describing its incidence as a proportion of all CHD. In a recent study from Denmark, the overall CHD birth prevalence, have been reported to have increased [7] from 73 to 113 per 10.000 live births from 1977 to 2005 with stabilization of the prevalence after 1996–1997. The increased prevalence was primarily due to an increase in VSD and ASD prevalence, related to improved diagnosis by echocardiography as reported by others [8,9,10,11]. The total prevalence of conotruncal defects, atrioventricular septal defects (AVSD), and right ventricular outflow obstruction (RVOTO) increased also significantly [7, 8], probably due to changes in the pregnancy risk factors particularly the increasing incidence of type 2 diabetes among women of childbearing age [7,12].

#### **IMPACT OF FETAL DIAGNOSIS OF CHD**

Fetal diagnosis of structural heart defects by ultrasound ranges from 8% in eastern Europe to 48% in France [4] due to an active policy in prenatal screening and involvement of obstetricians and sonographers in screening for cardiac

**\*Address Correspondence to Maurice Guirgis:** University Paris VII,Service Explorations Fonctionnelles, Hôpital Robert Debré, 48 bd Serurier 75019 Paris France; Email<EMAIL_ADDRESS>
malformations during routine obstetrical ultrasounds. This may have a potential impact on the incidence of CHD if termination of pregnancy is decided [4,13, 14]. In a study including 2454 cases with CHD, collected from 20 registries of congenital malformations in 12 European countries, termination of pregnancy was performed in 293 cases [12%) varying from 0% to 49% according to the registry [4]. In a recent analysis obtained from the Paris registry of congenital malformations, Koshnood et al. [5], reported increase rate of termination of pregnancy for cases with hypoplastic left heart syndrome (HLHS) detected by fetal echocardiography, that increased from 13.6%, between 1983-1988 to 72.4% between 1989-1994, before reaching a rate of 63% between 1995- 2000. Further studies are required to assess the impact of fetal medicine in the prevalence and outcome of CHD.

# **GEOGRAPHIC, RACIAL, ETHNIC & SOCIO-ECONOMIC DISTRIBUTION OF CHD**

The reported incidence of various cardiac defects may vary according to different geographic regions [11, 15-17] probably related to genetic and racial factors. For example, studies of ethnic influence on the pattern of CHD in the United Kingdom revealed a higher incidence of left obstructive disease such as aortic stenosis (AS) and coarctation of aorta (Ao Coa) in non-Asian (9%) than Asian (3%) infants [15]. This was also reported from epidemiologic studies from Saudi Arabia [11] and Japan [16], where a low incidence of AS and Ao Coa was reported (4.8% and 3.7% respectively of all patients with CHD) contrasting with a higher incidence reported from Europe [17]. A low incidence of AVSD was also reported from Japan [16] contrasting with a higher incidence in United Kingdom [15].

Compared with black infants, white infants have been found to have an increased prevalence of Ebstein's anomaly, AS, Pulmonary atresia, AVSD, ASD, Ao Coa, Transposition of great arteries (TGA) and Tetralogy of Fallot (TOF), while less white infants were found among cases with Pulmonary stenosis (PS) and heterotaxia [18]. These results highlight racial variations in CHD and may suggest that socio-economic status (SES) account for some of this variation, as also evidenced by an increased risk for TGA reported with low SES that included mother's education, poverty, and unemployment [19].

# **SEX DISTRIBUTION**

As regards sex distribution of CHD; some lesions such as Ao Coa, AS, TGA show strong male predominance [11, 20-21]. On the other hand, female predominance is observed in PDA, ASD, AVSD and PS [20, 21]. Gensburg et al [22], classifying isolated lesions according to the time of embryonic disturbed organogenesis, found male predominance in those lesions developing in later gestation.

# **ETIOLOGY OF CHD**

Cardiovascular development involves a series of complex events precisely orchestrated and regulated by specific genes. CHD represent multiple underlying etiologies: genetic, environmental, teratogenic exposures, multifactorial and unkown mechanisms.

The precise links between genetic and environmental factors, are incompletely understood. Environmental factors may affect gene expression directly or may block the action of gene product. Some outflow tract (Truncus Arteriosus, Double outlet right ventricle) that may be associated with the DiGeorge (CATCH 22 syndrome) may result also from interfering with migration of neural crest cells by certain chemicals (bis-diamine, tran-retinoic acid), or by experimentally removal of cranial neural crest cells [23].

The current state of knowledge on genetic causes of CHD [24] is reviewed separately in another chapter. Environmental factors involved in the etiology of CHD are multiple and include maternal diseases, drug exposures, alcohol, and other environmental exposures [24,25,26]. The potential factors that might influence the risk for CHD including periconceptional folic acid intake which may reduce the risk [27-29] and those factors that increase the risk for CHD are discussed.

### **ROLE OF MULTIVITAMINS AND FOLIC ACID**

Periconceptional intake of multivitamins supplements containing folic acid [27,28] was reported to possibly reduce the risk of CHD up to 60% [27]. In a recent work [29], fortification of grain products with folic acid in Canada, was followed by a significant decrease in the birth prevalence of severe CHD strongly supporting the protective effect of Folic acid. Specifically, the birth prevalence did not change in the eight years before fortification and decreased in the seven years after fortification with a significant change in time trend between the two periods for conotruncal defects and non-conotruncal defects [29].

# **MATERNAL DISEASES AND CONDITIONS**

# **MATERNAL DIABETES**

CHD is found in 3-5% of pregnant women with maternal pregestational diabetes [30-32]. Associations of CHD with gestational diabetes are probably due to inclusion of pregnant women with previously undetected type 2 diabetes among those classified as having gestational diabetes. Almost all cardiac lesions have been reported, mainly outflow tract lesions, conotruncal anomalies, AVSD, TGA, VSD, HLHS and Ao Coa [30-32]. Cardiac malformation occurs before the seventh week of gestation possibly by abnormal glucose level affecting the expression of a regulatory gene in the embryo, leading to apoptotic cellular changes [32]. Another possible mechanism is the generation of free radicals resulting from metabolic abnormalities as suggested by prevention of diabetic embryopathy in animal studies by antioxidants [33-34].

# **Phenylketonuria**

Maternal phenylketonuria is associated with increased risk of heart defects through increased blood levels of phenylalanine and phenyl pyruvic acid [35,36]. The most frequent defects are TOF, Ao Coa, VSD, PDA, Single ventricle, and ASD. Diet control before conception and during pregnancy reduces the risk of CHD [36].

Rubella, Febrile Illnesses, and Influenza Maternal rubella infection during pregnancy can result in increased incidence of CHD about 35% [37-39]. Common reported defects are PS, PDA, VSD, PPS, and VSD [40,41]. Maternal febrile illnesses, influenza, during the first trimester of pregnancy, may also be associated with an increased risk for certain heart defects such as conotruncal lesions, right and left obstructive lesions , VSD and Ao Coa [42- 44].

## **Maternal HIV**

Children infected with HIV-1 has not been reported to be associated with an increased risk of CHD. [45]. Irrespective of their HIV-1 status, infants born to women infected with HIV-1 have significantly worse cardiac function than other infants [45-46].

## **Maternal Stress**

Intense maternal stress (e.g. divorce, death of a relative,..) during the periconceptional period was associated with increased risk of delivering infants with certain congenital anomalies particularly with conotruncal heart defects and neural tube defects [47, 48].

# **MATERNAL DRUG INTAKE**

Table **1** summarizes main maternal drug exposure -during the first trimester of pregnancy and periconceptional period - associated with CHD [24-26, 48-55].

**Table 1:** MATERNAL DRUG INTAKE AND CHD . Data from references [24, 25, 26, 48-55]

\*TAPVR: Total Anomalous pulmonary Venous Return

#### **4** *Four Dimensional Fetal Echocardiography Maurice Guirgis*

Some of the drugs were reported with associated risks of CHD, but only limited information is available e.g. Angiotensin –converting enzymes [49], Trimethoprim-Sulfonamide [50-51], metronidazole [24] , fluconazole [52,53].

# **OTHER MATERNAL NON THERAPEUTIC & ENVIRONMENTAL EXPOSURE**

### A**lcohol**

Several studies have reported teratogenic effects of alcohol consumption during pregnancy, including cardiac defects [56]. A more recent case-control study that examined the risk of congenital anomalies with different sporadic and daily doses of alcohol consumption in spain, reported an increased risk of CHD only with the highest level of maternal consumption of alcohol per day [57].

# **Cocaine and Marijuana**

Maternal cocaine ingestion was reported to induce coronary thrombosis in the developing fetal heart leading to single ventricle [58]. Association of maternal intake of cocaine with other defects was also reported : Ebstein's anomaly , VSD, heterotaxy [ 24,59, 60].

# **Cigarette Smoking**

The relationship between gestational smoking and congenital defects has been studied, however the information is inconclusive. Some studies have reported associations of maternal smoking with ASD, AVSD, TOF [61], however, no associations were found in other reports [24,62]. Further research on large population-based studiesis required to clarify this relationship.

## **Organic Solvents**

Some studies reported increased risk of TGA, HLHS, Ao Coa, TOF, PS with maternal exposure to solvents and paints [24]. However the precise links are difficult to clarify, because the composition varies between different commercial preparations.

### **Pesticides & Other Toxic Substances**

In the Baltimore-Washington Infant Study (BWIS), potential exposure to herbicides and rodenticides was associated with an increased risk of TGA, while potential exposure to pesticides was associated with TAPVR and VSD [24]. A more recent case-control study of various end-product uses reported an increased risk of conotruncal defects with maternal reports of exposure to insecticides [63].

### **Air Pollution**

Gilboa et al [64], observed positive associations between carbon monoxide and isolated ASD, TOF, particulate matter <10 µm in aerodynamic diameter and isolated ASD as well as between ozone and VSD. Further studies are also required to clarify if air pollution exposure influences the risk for CHD.

# **Maternal Home Tape Water Consumption**

A positive association between a mother's consumption of home tap water during the first trimester of pregnancy and cardiac anomalies. This was unrelated to water contamination, mother's race, or her educational level [65].

#### **Waste Sites and Ionizing Radiation**

Much of the recent evidence about possible increase risk of CHD in communities situated near hazardous waste sites are inconsistent [66] and may not ultimately prove to be causal. Few reports on possible associations of CHD with maternal exposure to ionizing radiation in occupational settings or as part of medical or dental evaluations, found no clear evidence of any associations [24], and further studies are also required to clarify the precise relationship between these factors and CHD.

# **CONCLUSION**

CHD is associated with a considerable disease burden at both country and individual levels. Although there is a substantial variation in the reported prevalence of CHD in the literature, due to differences in epidemiological studies, however recent studies suggest an increased prevalence of CHD, mainly by increased incidence of small lesions easily detectable by echocardiography, as well as increased prevalence of conontruncal and atrioventricular septal defects.

Fetal diagnosis of CHD may affect the prevalence and the outcome of CHD. The impact of fetal diagnosis on prevalence, and outcome of CHD requires further investigations as there is no available uniform parental counselling and ethical guidelines.

Prevention of CHD is actually limited to our actual knowledge of the proportion of CHD attributable to non inherited potentially modifiable environmental fetal exposure, that although difficult to estimate, may account for 13.6% to 30.2% of cases [26].

Further epidemiological studies, based on large population-based studies, using more standardized case ascertainment and classification methods are required, to unmask some of the mysteries of abnormal cardiogenesis and clarify the precise links between inherited and non inherited risk factors and CHD, in order to be able to develop adequate prevention strategies.

## **REFERENCES**

© 2010 The Author(s). Published by Bentham Science Publisher. This is an open access chapter published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

# **CHAPTER 2**

# **Second Trimester Screening of Congenital Heart Disease**

# **Giovanna Oggè, Pietro Gaglioti, Manuela Oberto and Tullia Todros\***

*Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Unit, University of Turin, Italy*

**Abstract**: Congenital heart diseases (CHD) are frequent fetal anomalies, with an important impact on perinatal mortality and morbidity. Prenatal diagnosis has a demonstrated effect in decreasing the overall prevalence at birth, and in improving the outcomes of specific malformations; moreover, the great majority of these malformations occurs in the absence of any risk factor. All of these features strongly evidence the need for a screening test that can be applied to the general population, to identify a selected group of fetuses for the more specific, complex, and time-consuming diagnostic test (fetal echocardiography). The systematic visualization of the four chamber view and the outflow tracts during routine anatomical scan has progressively increased the prenatal detection rate of CHD. However, a number of potentially diagnosable defects are still missed in the screening setting. Three-dimensional ultrasonography could provide a useful tool to ameliorate the current performance of CHD screening; however this possibility needs to be further explored.

**Key Words**: Congeniral Heart Disease, Diagnosis, Fetal Echocardiography, Screening.

#### **INTRODUCTION**

Congenital heart diseases (CHD) are the most common congenital anomalies, with a prevalence of around 9/1000 livebirth [1]; moreover they account for the majority of infant deaths due to congenital malformations [2, 3].

Prenatal diagnosis of CHD implies a number of potential advantages: 1) if it is early enough during gestation, it allows consideration of termination of pregnancy [4]; 2) it consents the planning and timing of delivery in a referral centre, leading to better conditions at surgery; 3) it permits *in utero* treatment, although, to date, few procedures have been performed (ballon valvuloplasty for aortic or pulmonary stenosis [5, 6], atrial septoplasty for hypoplastic left ventricle with resctrictive foramen ovale [7-9], cardiocentesis for pericardial effusion [10-15]) and available data are too sparse to attest a benefit [16, 17]. In contrast, pharmacological transplacental therapy for fetal arrhythmias has become a well accepted practice, based on a consistent body of evidence [18].

Although several risk factors for the development of CHD are recognized (see Table 1), the great majority of these malformations are diagnosed in low-risk pregnancies [19]. This enhances the need for a screening test, which ideally should be simple and rapid enough to be systematically applied to the general population, to identify cases eligible for fetal echocardiography [20, 21]. The usefulness of a systematic screening program is further confirmed by the fact that the majority of prenatal diagnoses of CHD actually occur in women who have been referred to echocardiography because of a suspicion at the screening exam [22].

**Family history** First-degree relative of proband **Maternal diseases**  Pregestational diabetes mellitus Phenylketonuria Autoimmune diseases: anti-Ro (SSA) and anti-La (SSB) **Maternal infections**  Parvovirus B19 Rubeovirus Coxsackie virus

**Table 1:** Risk factors for CHD (indications for fetal echocardiography). Modified from [23].

**\*Address correspondence to Tullia Todros:** Department of Obstetrics and Gynecology, University of Turin, Ospedale S Anna Corso Spezia, 60, 10126 Torino Italy; Email<EMAIL_ADDRESS>
#### **Table 1: cont....**

The first significant effect of prenatal diagnosis of CHD has been the reduction of the prevalence of these anomalies at birth, secondary to increased termination of affected pregnancies. The proportion of termination of pregnancies, among prenatally diagnosed CHD, is 50% [24], and an increase in the number of anomalies diagnosed *in utero* as well an anticipation of the diagnoses is likely to augment the absolute number of terminated pregnancies.

Contrary to the expectations, a positive impact of prenatal diagnosis on the overall survival rate of neonates with CHD has not been demonstrated [25]. One explanation is that prenatally diagnosed CHD tend to be more severe than those diagnosed postnatally, and they are more frequently associated with chromosomal and extra-cardiac anomalies, that negatively influence their prognosis [26].

However, a positive impact of prenatal diagnosis on neonatal outcomes has been demonstrated for specific CHD, namely aortic coartation [27], transposition of great arteries [28], hypoplastic left heart syndrome [29, 30].

#### **THE FOUR CHAMBER VIEW**

A first screening test for CHD was proposed in the 80's, and it was based on the inclusion of the four chamber view in all routine ultrasound performed since 16 weeks of gestational age [31].

The main advantage of such a method is the possibility to examine several cardiac structures in one single ultrasonographic plane. Indeed, the correct visualization of the four chamber view, either from an apical or from a transverse approach, allows the evaluation of [32].

*(see Figures 1 - 4).*

**Figure 1:** a) Transverse section of the fetal abdomen: the stomach (ST) is on the left side; the transverse sections of the descending aorta (AO) and inferior vena cava (IVC) are in front of the spine (S), at the left and at the right respectively. The intrahaepatic portion of the umbilical vein (UV) is also seen in this section.

**Figure 2**: Transverse section of fetal thorax: the longitudinal axis of the heart (dashed line) forms an angle of about 45° with respect to the antero-posterior axis (AP) of the thorax. The apex of the heart is on the left. LV: left ventricle; RA: right atrium; S: spine.

**Figure 3:** Apical four chamber view: a) the septal leaflet of the tricuspid valve (TV) has a more apical insertion on the interventricular septum (IVS) than the mitral valve (MV); b) pulmonary veins draining in left atrium.

**Figure 4**: Transverse four chambers view: the apex of the heart is at the left of the fetal thorax. a) the interventricular septum and the walls of the ventricles are better visualized than in the apical view. b) the thickness of the ventricular walls (red lines) and septum (IVS) can be studied. The valve of the foramen ovale (arrow) moves toward the left atrium. LA: left atrium; LV: left ventricle; RV: right ventricle; RA: right atrium; FO: foramen ovale.

b) transverse section of the fetal thorax: transverse section of the descending aorta (AO) and apical four chamber view of the heart. LA: left atrium; LV: left ventricle; RV: right ventricle; RA:right atrium

Hence, the visualization of the four chamber view allows the detection of the wide range of CHD that directly or indirectly modify the above mentioned anatomical structures (see Table 2).

The first reports on the diagnostic accuracy of the four chamber view showed very encouraging results, with sensitivities ranging form 70 to 90%, thus promoting its wide diffusion [31-34]. However, several subsequent studies provided sensitivity values lower then 30% [35-37].

Many factors account for the discrepancies in the detection rate of the four chamber view, including:

Indeed, the first and more promising results came from studies that were performed in referral centres, on high-risk or unselected populations, and by highly specialized operators [31, 32], while the more disappointing results were from multicentric studies, on low-risk populations, and thus better reflect the efficacy on the field of the screening intervention [35, 36].

#### **THE OUTFLOW TRACTS VIEWS**

The main limitation of the four chamber view lies in the impossibility to detect anomalies affecting the ventriclearterial connections, unless they indirectly alter the morphology of the cardiac chambers or the cardiac axis (see Table 2). Importantly, this group of CHD includes conditions, such as transposition of the great arteries, which require early neonatal intervention, and therefore would receive the greatest advantage from accurate prenatal diagnosis. Therefore several investigators suggested to add to the four-chamber view the visualisation of the left ventricular outflow tract (five chamber view) [38, 39], or the visualisation of both outflow tracts[40-43].

#### **12** *Four Dimensional Fetal Echocardiography Oggè et al.*

The outflow tracts can be evaluated both by the left ventricle and right ventricle "long axis" views and by the "short axis" view [44] (see Figures 5 – 7)

**Figure 5:** left ventricle long axis view: note the continuity of the aorta anterior wall (arrowhead) with the interventricular septum (IVS) and the continuity of the aorta posterior wall with the anterior leaflet of the mitral valve (MV) (arrow). LA: left atrium. LV: left ventricle; Ao: aorta. RV: right ventricle.

**Figure 6**: right ventricle long axis view: the pulmonary artery (PA) originates from the infundibular portion of the right ventricle (RV). PV: pulmonary valve; LV: left ventricle

**Figure 7** Longitudinal section of the fetal thorax. Short axis view of the great vessels: the aorta (Ao) is in the centre, in transverse section, while the pulmonary artery is visualized in a longitudinal plane, arising from the right ventricle (RV) and in continuity

#### *Second Trimester Screening of Congenital Heart Disease Four Dimensional Fetal Echocardiography* **13**

with the ductus arteriosus (D). The right pulmonary artery is also displayed (arrowhead). RA: right atrium; TV: tricuspid valve; PA: pulmonary artery; PV: pulmonary valve.

The long axis views allow visualizing the aorta and the pulmonary artery, with approximately equal diameters, emerging from left and right ventricle respectively, and crossing at about a 70° angle just above their origin. The aorta originates from the more posterior ventricle; its anterior wall is in continuity with the ventricular septum, while its posterior wall is in continuity with the anterior leaflet of the mitral valve. The pulmonary artery originates from the more anterior ventricle, and bifurcates into the right pulmonary artery and the ductus arteriosus.

Other authors suggested to include the "three vessels and trachea" view into the screening exam of the fetal heart (see Fig. 8).

**Figure 8**: the three vessels can be seen with transverse sections of the fetal thorax above the heart. a) from left to right: pulmonary artery (P), aorta (Ao), superior vena cava (SVC). Note the thymus between the three vessels and the anterior wall of the thorax. b) Moving cranially from the three vessels view, making a slight caudal tilt of the ultrasound beam to the left, allows the aortic arch (AoA) and duct (DA) to be imaged simultaneously.

#### **DAo: Descending Aorta; T: Trachea**

This latter is a transverse thorax plane, which permits to verify the presence, position and size of the pulmonary artery, the ascending aorta and the superior vena cava [45], and is considered equally informative with regards to the anatomy of the great vessels compared with the outflow tracts, but more easy to obtain. Several studies have shown that the routine visualization of the outflow tracts – the "extended- basic" cardiac scan [22] – actually increases the sensitivity of the four chamber view. Although once again the highest detection rates come from studies conducted in referral centres and on the high-risk population [19, 45]. nonetheless even multicentric studies on the low-risk population could demonstrate a significant benefit compared with the four chamber view alone [46, 47].

**Table 2:** CHD and prenatal diagnosis

#### **CHD usually associated with abnormal four-chamber view**

1) *Heart abnormalities with a direct effect on the anatomy of the cardiac chambers* Hypoplastic left heart syndrome Hypoplastic right heart syndrome Atrioventricular septal defects Large ventricular septal defects Atrio-ventricular valve abnormalities Ebstein's anomaly Double inlet ventricle 2) *Abnormalities of the great vessels with an indirect effect on the symmetry of the cardiac chambers*  Severe aortic coarctation Severe aortic stenosis Severe pulmonary stenosis or pulmonary atresia with intact interventricular septum

3) *Abnormalities of the situs*

4) *Myocardial hypertrophy*

5) *Cardiac tumors*

6) *Pericardial effusions*

#### **CHD usually not associated with abnormal four-chamber view**

Patent ductus arteriosus

#### **EARLY SCREENING**

The fetal heart is completely formed 56 days after conception (10 weeks of postconceptional age, i.e. 8 weeks of gestational age). As a result of the rapid advances in the resolution power of ultrasound machines, a growing number of reports have gathered since the early 90's, showing the feasibility of examination of the fetal heart early in gestation [48-54].

The advantages of a reliable early test are intuitive: in high risk pregnancies, the confirmation of normal cardiac anatomy would reduce maternal anxiety, while the early recognition of a severe CHD would allow the termination of pregnancy in safer conditions, and would provide a longer temporal window for karyotyping, multidisciplinary counselling, the couple's decision-making, and the planning of the pregnancy's and neonatal care. However, although the feasibility of the echocardiografic study at 12-13 weeks of gestational age, by specialized operators and in high-risk pregnancies, is well demonstrated, there is no solid evidence to-date to support the advantage of the anticipation of the cardiac fetal screening in the low-risk population [55].

#### **THE ROLE OF NUCHAL TRANSLUCENCY IN PRENATAL SCREENING OF CHD**

The measurement of nuchal translucency (NT) between 11 and 14 weeks of gestational age is a widely diffuse screening test for chromosomal anomalies. In addition, an association between increased NT and CHD, in the absence of chromosomal defects, has been demonstrated, suggesting a potential role for NT as an early screening test for CHD [56-68] . Several studies designed to assess the accuracy of this screening approach have reported very heterogenic results, partly due to the differences in the prospective or retrospective study design, and the extent of the postnatal follow-up (see [69] for review). However, the most recent studies tend to evidence quite a low detection rate: the adoption of a cut-off of 2.5 multiple of the median (MoM), approximately corresponding to the 99th percentile for gestational age, allows the identification of 7% of all the CHD and 13.5% of major CHD, with 1% of the population undergoing echocardiography [70]. These data, which are definitely disappointing, compared with the midtrimester "extended basic" scan, do not justify the adoption of NT as a screening test for the general population. However, the finding of increased NT (≥ 2.5 MoM) during the aneuploidies screening test, should be considered as an indication for fetal echocardiography.

# **IMPORTANCE OF TRAINING**

There is solid evidence that the sensitivity of the prenatal screening of CHD is strongly dependent not only on the number of sonographic views, but also on the operator's experience. The systematic adoption of a training program for the visualization of the four chamber view and the outflow tracts view in Northern England, has increased the proportion of severe CHD that were diagnosed *in utero* from 17 to 30% [71]. A recent Norwegian study [72] measured the accuracy of second trimester ultrasound performed by sonographers and midwives in diagnosing CHD in an unselected population: they found that more experienced operators (who had carried more than 2000 routine scans) were more likely to obtain both four chamber view and outflow tracts view than less experienced operators (75% vs 36% of cases); as expected, this difference was associated with a significantly better detection rate of major heart defects (52% vs. 32.5%).

# **ROLE OF 3D ULTRASOUND IN THE PRENATAL SCREENING OF CHD**

The prenatal screening for CHD is a promising field of application for 3D ultrasound, which still needs to be adequately explored. Indeed, many of the peculiar characteristics of 3D sonography make it an ideal tool for the screening setting. The possibility to reconstruct offline virtually any different plane from a single acquired volume, makes this technology more efficient, reducing the time needed per each single exam; the advantage in term of time saved (which implies the possibility to examine a greater number of subjects) appears to be significant even after considering the additional time needed for the offline manipulation and interpretation of volumes [73-77].

A precious feature of 3D ultrasound is the feasibility to reconstruct offline planes that were not acquired during the patient examination, therefore making the sonogram less operator-dependent [73,74,75] (see Fig 9).

A further advantage of the use of 3D ultrasound as a screening tool, is the opportunity to send the acquired volumes to a referral centre for evaluation in the case of a suspicion of malformation, without any need to move the patient.

The other face of the coin, however, is the new set of skills that have to be acquired by the operator, in order to obtain good informative volumes, minimize artifacts, and interpret the reconstructed planes [58].

On the basis of these considerations, several studies have been conducted to demonstrate the feasibility of the midtrimester anatomic screening survey, demonstrating a good degree of agreement between the 3D and the 2D sonographic examination [74, 75, 77].

The application of these concepts to the screening of CHD is partly limited by the peculiarity of the motion of this organ, which clearly increases the risk of artifacts. Moreover, the evaluation of cardiac function and rhythm relies on the assessment of real-time scans. However, the possibility to study the moving heart (but not to evaluate the heart rhythm) has been overcome, to a certain extent, by the introduction of the spatio-temporal correlation image technique (STIC).

One claimed benefit of 3D technology is that the acquisition of a single volume dataset allows the visualization of other planes that might be technically more difficult to obtain. When considering the standard exam of the fetal heart, the acquisition of a cardiac volume from the chamber view, can therefore allow the visualization of the more challenging outflow tracts views[78]. Paladini *et al* [79] have recently addressed this issue by assessing the diagnostic accuracy in the evaluation of the outflow tracts using STIC volumes acquired from the four-chamber view. In this study, a group of 14 sonologists of low-to-intermediate experience in basic cardiac scanning, were given a short training in the evaluation of the outflow tracts and volume manipulation; immediately after, they were asked to examine offline 26 volumes, acquired from the four chamber view between 19 and 23 weeks of gestational age, including 16 normal cases and 10 with conotruncal anomalies. Overall sensitivity was 83%, specificity 87% positive predictive value 80% and negative predictive value 89%; the sensitivity per each single anomaly ranged from 50% for transposition of great arteries with intact ventricular septum, to 100% for double outlet right ventricle with or without pulmonary atresia, and transposition of great arteries with ventricular septal defect. However, the study was not designed to evaluate the ability of the sonologists to acquire volumes of adequate quality, and to recognize and discard those of poor quality. Maybe more importantly, the high prevalence of CHD in the study population (38%) prevents the application of these results to the general population.

In summary, three-dimensional ultrasonography possess many characteristics to become a useful tool for the screening of CHD (as well as other malformations). However, before it can be adopted in the general practice, protocols, indications, and terminology should be further standardized and accepted. Moreover, a learning curve should be anticipated, and education and training should be systematically provided to allow the operators to achieve the new skills.

## **REFERENCES**

#### *Second Trimester Screening of Congenital Heart Disease Four Dimensional Fetal Echocardiography* **19**

© 2010 The Author(s). Published by Bentham Science Publisher. This is an open access chapter published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

# **The Examination of the Normal Fetal Heart**

# **Alessandra Toscano, Luciano Pasquini\* and Roberta Iacobelli**

*Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesu' Hospital, Rome, Italy*

**Abstract**: The heart, anatomically and embryologically, is a segmented structure. The atria, the ventricles and the great arteries are the three major fundamental components. The heart should be examined echocardiographically by Sequential Segmental Analysis from the venous to the arterial poles following the blood flow. Each segment is evaluated independently considering not only the segmental situs (or location into the body) but also the connections of each heart segment to the others. A systematic approach by Sequential Segmental Analysis is a cornerstone of fetal cardiac study. First step is the identification of fetal heart position followed by the identification of position of the heart in relation to the body and the anatomic study of each cardiac chamber, and finally, the study of cardiac rhythms and function. The heart can be observed in infinity of planes, but few sections are the basis of fetal cardiac study. The examination starts with abdominal cross-sectional view for the identification of the viscero-atrial situs. Then the transthoracic four-chamber view should be obtained. This view allows to obtains a large amount of informations specially regarding the atria and ventricles, atrioventricular valves, interatrial and interventricular septum. Ventriculo-arterial connections are well identified by a gentle sweep towards the fetal neck, left ventricular outflow tract and ascending aorta are first visualized and, by further sweeping, also right ventricular outflow tract, branch pulmonary arteries and ductus arteriosus are correctly identified. The three vessel view give us information regarding left or right location of aortic arch. Short axis of the heart is evaluated from the cavo-atrial and ventricular segments to the ductal and aortic arches. Finally the study of heart rate and rhythm and of myocardial function ends the fetal heart examination.

**Key Words**: Fetal Heart, Ultrasound, Diagnostic Planes, Segmental Analysis

#### **FETAL CARDIAC ANATOMY**

The heart should be examined ultrasonographically by sequential segmental analysis starrting from the venous and finishing at the arterial poles [1]. It is helpful to consider the heart as a segmented structure represented by three regions: atria, ventricles, and great arteries [2]. The two connecting cardiac segments are the atrioventricular canal or junction and the infundibulum or conus arteriosus. Each region, in turn, is partitioned into two components, usually right-sided and left-sided. There are only a limited number of possible connections between the three major regions, regardless of their spatial orientations. In practice, each region is evaluated independently, following the direction of blood flow: systemic and pulmonary veins, atria, atrioventricular valves, ventricles and right ventricular outflow tract, semilunar valves, and great arteries. In a systematic manner, right-sided and left-sided structures at each level are evaluated according to their morphology, their positions and connections to segments. The diagnostic problem generated by congenital heart disease is that the morphologically or anatomically right atrium, left atrium, right ventricle, and left ventricle can from the positional standpoint be "anywhere". Morphologic anatomic identification is the cornerstone of accurate diagnosis. It starts with the identification of readily recognizable landmarks and progresses to more subtle findings. The step-by-step approach that we use includes: the identification of the fetal position, the position of the heart in relation to the body, the number of chambers and their connections, and finally, the rhythm.

#### **POSITION OF THE FETUS IN THE UTERUS**

Correct prenatal determination of the fetal right/left axis is essential for the diagnosis of fetal malformations, in particular congenital heart anomalies. To assess the cardiac position in the uterus, observe the fetal position: is it cephalic or breech? Then identify the position of the spine and of the cardiac apex (Clip 1).

#### **LOCATION IN THE CHEST**

With regard to the position of the heart in the chest, two questions arise that can be answered: where is the heart

**<sup>\*</sup>Address correspondence to Luciano Pasquini:** Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesu' Hospital, Piazza S.Onofrio, 4 - 00165 Rome Italy; Email<EMAIL_ADDRESS>
located, and what is the direction of the cardiac apex? Within the thorax, the heart can be described as left-sided (normal), right-sided, or in a midline position. The position of the heart in the mediastinum is affected not only by underlying cardiac malformations but also by abnormalities in adjacent structures. Some hearts are abnormally displaced from their usual position in the anterior left central chest. This abnormal cardiac position can be caused by a diaphragmatic hernia or space-occupying lesion, such as cystic adenomatoid malformation. Position abnormalities can also be secondary to fetal lung hypoplasia or agenesis. Rightward displacement of the heart constitutes dextroposition, a leftward shift represents levoposition, and shifts toward the midline are called mesoposition.

## **ORIENTATION IN THE CHEST**

The left-right orientation of the abdominal organs and of the heart in vertebrate is a non random and highly conserved phenomenon [3], probably controlled by several genes [4,5,6,7]. Levocardia is the normal state and is caracterized by a ventricular apex that is directed leftward, anteriorly and somewhat inferiorly. In Dextrocardia, the apex is directed to the right of midline [8-11]. Mesocardia is the location of the heart with the cardiac base-apex axis directed to the midline of the thorax [12].

# **THE ATRIA**

There are two main type of visceroatrial situs (situs meaning location). Situs solitus, the normal pattern of anatomic organization in which the right atrium is right -sided and the left atrium is left-sided,. In situs inversus is present an inverted or mirror image pattern where the right atrium is left- sided and the left atrium is right- sided. Situs "ambiguus" indicates that the type of visceroatrial situs is anatomically uncertain or indeterminated, and it occurs in the heterotaxy syndrome with asplenia or polysplenia [13-15].

## **THE VENTRICLES**

There are two types of ventricular situs: D-loop ventricles, in which the morphologically right ventricle is typically right-sided, and the morphologically left ventricle is left-sided. L-loop ventricles, that is, inverted or mirror image ventricles in which the right ventricle is typically left-sided and left ventricle is right-sided [16].

#### **THE GREAT ARTERIES**

Solitus Normally Related (the usual normal), Inverted Normally Related (mirror image), Malposition of the Aorta (anterior to the pulmonary artery): D (anterior and right), L (anterior and left), A (just anterior) [17].

# **FETAL ECHOCARDIOGRAPHIC PROJECTIONS**

The heart can be observed in infinity of planes, but few sections are the basis on which most of the diagnoses are made [18]. The basic cardiac screening examination relies on at least five transverse images of the heart and vasculature and three sagittal images [19,20].

### **ABDOMINAL CROSS-SECTIONAL VIEW**

The stomach should be seen on the left side of the fetus and just below the heart and diaphragm. It is important to localize the spine and the transverse descending aorta, which is a circle laying anterior to the spine. Usually in a normal fetus the descending aorta is in the left side and points to the left atrium (Clip 2).

# **TRANSTHORACIC FOUR CHAMBER VIEW**

The four-chamber view is generally easy to achieve and is useful for identifying the atria, ventricles, and respective septae [21]. A normal heart is usually no larger than one-third the area of the chest (Clip 3). The majority of the heart is in left chest. The heart is normally deviated about 45 ± 20◦ (2 standard deviations) toward the left side of the fetus (Fig. **1**). Situs abnormalities should be suspected when the fetal heart and/or stomach is/are not found on the left side as well. The atria should have equal size and thickeness. From the standard 4-chamber view, one should sweep posteriorly to demonstrate the coronary sinus (Clip 4). The right atrium is anteror and the left posterior. The left atrium is related to the descending aorta posteriorly. The morphologic features of the atrial appendages are usually appreciable only when the atria are outlined by excessive pericardial fluid. The interatrial septum is open at the level of the *foramen ovale*. The *foramen ovale* flap is visible in the left atrium, beating toward the left side [22]. The *foramen ovale* occupies about one third of the atrial septum. The flap valve has a biphasic motion during the cardiac cycle, partially closing at end systole and during atrial contraction end diastole. In the right atrium, two thin lines distinct from the interatrial septum can occasionally be seen. The Eustachian valve, a crest between the inferior vena cava and the wall of the right atrium, is located close to the inferior vena cava. The Chiari network is composed of abnormal lacelike strands that attach to the Eustachian valve and the *crista terminalis*. It results from the incomplete reabsorption of the *septum spurium*, which should be completed by the 3rd month and persists in about 1% of patients. The confluence of the pulmonary venous connections to the back of the left atrium should be identified. Exception: anomalous venous return. In the four-chamber view the most anterior vein is the inferior pulmonary vein; the most posterior is the superior pulmonary vein. To confirm an apparently normal pulmonary venous connection to the left atrium, forward flow from the vein in the pulmonary parenchyma into the atrium should be documented on color flow mapping (Clip 5), and ideally adding pulsed wave doppler. The normal pulmonary venous pulsed Doppler tracing shows forward flow throughout systole and early diastole with occasionally reversal of flow in late diastole. The flow pattern reflects left atrial events, the "suction" effect of atrial relaxation, followed by descent of the mitral valve orifice, late systole, passive opening of the mitral valve, early diastole, and atrial contraction that may cause minimal flow reversal in late ventricular diastole.

In the second trimester, the ventricles should be approximately equal in size, however, it is important to note that in later gestation, the right ventricle becomes slightly larger than left and should not be confused with pathologic right ventricular dilation [23, 24]. The right ventricle is the most anterior structure and closest to the anterior chest wall. The insertion of the tricuspid valve along the interventricular septum is more apical than the insertion of the mitral valve. The right ventricular apex should contain the moderator band, causing the apex to appear "filled in" (Clip 6). In favorable cases one can note the difference in lining of the two ventricles: the right ventricle has a more coarse lining than the left due to a coarser trabeculation. The left side of the interventricular septum is free of papillary muscle while a papillary muscle, implants on the septum in the right ventricle (i.e. the muscle of the septal leaflet of the tricuspid valve). In the left ventricle there are two papillary muscles in the left ventricle, while in the right ventricle three papillary muscles are prensent. The valve follows the ventricle, thus a bicuspid valve is an indicator of left ventricle, while a tricuspid valve marks a right ventricle. In a normal fetus, there is no atrioventricular valve regurgitation.

Doppler echocardiography may prove to be useful as an adjunct to imaging echocardiography for evaluation of fetal cardiac anatomy and function.

Doppler velocity measurements were obtained by placing the Doppler sample volume immediately distal to the valve leaflets in the ventricle. Using pulsed Doppler, there is a typical biphasic shape of the diastolic flow velocity waveform with an early peak diastolic velocity (E) and a second peak during atrial contraction (A-wave); E is smaller than A, and the E : A ratio increases during pregnancy toward 1, to be inversed after birth. Fetal cardiac blood flow patterns differ from those in the neonate and the adult. Flow in the fetus results from simultaneous ejection from both right and left ventricles into the systemic circulation.

The diameters of the mitral and tricuspid valve annuli can be evaluated as well as the lengths of the left and right ventricles. Several reference limits for dimensional measures based on gestational age have been published [25, 26].

The ventricular septum should appear intact. The ventricular septum will appear thin and an area of dropout may been seen just below the atrioventricular valves when imaged from the apex (Clip 7, Fig. **2**). In an apical fourchamber view, caution should be taken not to confuse this artifact with a ventricular septal defect. Imaging from a lateral view perpendicular to the septum will better demonstrate its thickness and continuity. Small septal defects can be very difficult to confirm if the ultrasound imaging system fails to provide a sufficient degree of lateral resolution, especially if fetal size and position are unfavorable.

**Figure 1:** Fetal cardiac axis and position. LA, left atrium, LV, left ventricle, RA, right atrium, RV, right ventricle. The cardiac axis can be measured from a four-chamber view of the fetal heart.

**Figure 2:** Four- Chamber view of the fetal heart. LA, left atrium, LV, left ventricle, RA, right atrium, RV, right ventricle.

#### **CARDIAC LONG-AXIS VIEW**

The long-axis view is aligned with the left ventricular outflow tract (Clip 8, Fig. **3**). Evaluation of outflow tracts can increase the detection rates for major cardiac malformations above those achievable by the four-chamber view alone [27,28]. The four chamber view is inadequate for determining the conotruncus anomaly and in particular Transposition of the Great Arteries, Tetralogy of Fallot, Subaortic Ventricular Septal Defect, Double Outlet Right Ventricle, and Truncus Arteriosus. From the four-chamber view a slight cranial angulation of the transducer should reveal the left ventricular outflow tract the aortic valve and proximal ascending aorta, (also called the five-chamber view) (Clip 9). The left ventricular outflow tract view confirms the presence of a great vessel originating from the left ventricle. The continuity between the mitral and aortic valves and the absence of sub-aortic conus should be noted. The size of the ascending aorta can be measured. The anterior leaflet is in continuity with the posterior wall of the aorta. The anterior wall of the aorta is in continuity with the interventricular septum. The aortic valve and ascending aorta are seen arising centrally from the four- chamber view with the ascending aorta directed toward the right shoulder. The aortic valve moves freely and should not be thickened. For the arterial Doppler studies, the transducer must be positioned so that the sample volume is placed parallel to the flow. With pulsed Doppler, a single peak flow velocity waveform for the aortic valve should be demonstrated. The peak systolic velocity increases from 50 to 110 cm/s during the second half of pregnancy and it is higher across the aortic than the pulmonary valve. Time to peak velocity in the aorta is longer than in the pulmonary trunk. The ventricular output can be calculated by using the product of the valve area and mean velocity of flow, When the left ventricular outflow tract is truly the aorta, it should even be possible to trace the vessel into its arch, from which three arteries originate into the neck. The ventricular septum should appear intact from the apex to crux and from the apex to the anterior wall of the aorta.

**Figure 3:** Left ventricular outflow tract. LA, left atrium, LV, left ventricle, Ao, ascending aorta.

### **FOUR-CHAMBER SWEEP TO THE RIGHT VENTRICULAR OUTFLOW TRACT VIEW**

Continuing the sweep toward the fetal neck, a view of the right ventricular outflow tract documents the presence of a great vessel starting from a morphologic right ventricle. The pulmonary artery normally arises from the right ventricle and courses toward the left of the more posterior ascending aorta (Clip 10, Fig. **4**).

**Figure 4:** Right ventricular outflow tract. LV, left ventricle, RV, right ventricle. PA, pulmonary artery.

The bifurcation of the pulmonary artery and ductus arteriosus completes this view. The right ventricular outflow tract can be confirmed as a pulmonary artery only if its distal end appears bifurcated. The distal pulmonary artery normally divides toward the left side into a ductus arteriosus that continues into the descending aorta. The right side branch into the right pulmonary artery. The great arteries are similar in size, but the pulmonary artery at the valve ring may be slightly bigger than the aorta. The pulmonary valve is anterior and cranial to the aortic valve. The great arteries cross over at their origin.

#### **THE THREE-VESSEL VIEW**

Demonstrates the long axis views of the tranverse aortic arch and ductus arteriosus and the short axis views of the superior vena cava and trachea (Clip 11) [29-33].

#### **THE SHORT AXIS VIEW / THE RIGHT HEART VIEWS**

This section demonstrates the right ventricle and the ventricular outflow tract. The main pulmonary artery originates from the anterior ventricle and trifurcates into a large vessel, the ductus going into the descending aorta, and two small vessels, the pulmonary arteries. The pulmonary valve is anterior and cranial to the aortic valve. This is the best section to demonstrate the pulmonary valve (Clip 12, Fig. **5**).

**Figure 5:** Short-axis view. LA, left atrium, RA, right atrium, RV, right ventricle, PA, pulmonary artery, Ao, aorta.

### **DUCTAL AND AORTIC ARCH VIEW**

In a normal fetus, the aortic arch can be evaluated in both transverse and longitudinal views. The transverse view is more useful because the distal arch can be followed to its connection to the duct, and the two vessels can be directly compared in size, they should be equal in diameter. The longitudinal view shows the tight "hook" shape of the normal arch (Clip 13, Fig. **6**) [34-36]. The aortic arch is obtained with the beam aligned from anterior right of the fetal chest to posterior left of the fetal chest. The side of the aortic arch can be readily shown in fetal life, using the orizzontal view of the arch. The ductal view is obtained when the imaging plane is aligned with the right ventricular outflow tract and main pulmonary artery. In the ductal view, the main pulmonary artery, and ductal arch are well seen and main pulmonary artery size can be easily measured. The ductal arch is formed by the communication of the ductus arteriosus with the descending aorta, appears more flattened than the aortic arch and will have no head and neck vessels arising from it. Note laminar flow, direction, and velocity with color flow and spectral (pulsed wave) Doppler. Normal ductal velocities in 20- to 39-week fetuses range from 50 to 140 cm/sec in peak systole and 6 to 30 cm/sec in peak diastole. Premature ductal constriction is distinguished by either an increase in peak systolic and end diastolic velocities or absolute absence of flow in case of premature closure. Severe constriction leads to progressive right ventricular pressure overload, hydrops, and fetal death. Retrograde flow in the ductus arteriosus should prompt investigation for an right ventricular outflow tract obstruction.

**Figure 6:** Ductal view and aortic arch view. RV, right ventricle, PA, pulmonary artery, PD, ductus arteriosus, Ao, aortic arch, LA, left atrium.

#### **CAVAL LONG-AXIS VIEW**

The caval long-axis view is obtained with the imaging plane parallel to the caval connections to the right atrium. The superior vena cava and the inferior vena cava drain from a posterior position to a medial connection to the right atrium (Clip 14, Fig. **7**).

**Figure 7:** Caval long-axis view. LA, left atrium, SVC, superior vena cava, IVC, inferior vena cava, RA, right atrium.

#### **MYOCARDIAL FUNCTION**

An assessment of fetal cardiac function can be made using traditional M mode to provide information on wall thickness and ventricular shortening fraction. An m-mode set of measurements can be made with the beam set perpendicular to the lower half of the interventricular septum [37,38]. The function can be measured as a shortening fraction > 30% (diastole-systole/diastole). Diastolic functions is impaired when a fetal and a fully developed myocardium are compared, indicating that fetal myocardium is less compliant. Observations on the diastolic function of the human fetal myocardium are made by Doppler echocardiographic blood flow velocity profiles. In the human fetus, peak blood flow velocity is greater during active filling (atrial contraction) than during the rapid filling phase, because of the atriosystolic function. This finding indicates diminished ventricular compliance in the fetal heart [39]. The fetus has a limited range of heart rates over which cardiac outputs can be maintained. Prolonged extreme bradycardia (heart rate less than 50 beats/min) or tachycardia (heart rate higher than 200) is known to cause congestive heart failure and hydrops. Some investigators have stated that alterations in heart rate are the major determinants of cardiac output. The relationship between cardiac cycle length and stroke volume indicates that the major regulator of cardiac output in the human fetus is the Frank-Starling mechanism.

#### **HEART RATE**

Cardiac rate and regular rhythm should be confirmed. Fetal cardiac activity is detectable from 6 weeks on by suprapubic ultrasound and about one week earlier by transvaginal ultrasound. The normal fetal heart rate varies with gestational age. It is around 100 beats per minute (bpm) at 8 weeks, reaches 175 bpm by 10 weeks, 150 at 15 weeks and slows further to about 140 +- 20 bpm at 20 weeks and 130 + - 20 bpm at term. Mild bradycardia is transiently observed in normal second‐trimester fetuses. Fixed bradycardia, especially heart rates that remain below 110 beats per minute, requires timely evaluation for possible heart block. Mild tachycardia (*>*160 beats per minute) can occur as a normal variant during fetal movement. Persistent tachycardia, however, should be further evaluated for possible fetal distress or more serious tachydysrhythmias [40,41].

#### **REFERENCES**

© 2010 The Author(s). Published by Bentham Science Publisher. This is an open access chapter published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

# **CHAPTER 4**

# **Real Time Three Dimensional Fetal Echocardiography Using Two Dimensional Array Technology.**

**Dev Maulik\*, MD, PhD, David Mundy, MD and Timothy Bennett, MD**

*Department of Obstetrics and Gynecology, University of Missouri-Kansas City School Medicine, Kansas City, Missouri, USA*

**Abstract**: Three dimensional (3D) echocardiography represents a major paradigm shift in medical ultrasound imaging. As opposed to reconstructed 3D echocardiography which is based on a series of two dimensional images, the revolutionary development of the two dimensional (2D) matrix phased array transducer permits true real time live 3D imaging of the fetal heart. Preliminary experience has demonstrated that real time/live 3D echocardiography is not only feasible in assessing the fetal cardiac anomalies, it also permits unique comprehensive views of the fetal heart that are unattainable with 2D echocardiography. With further evolution of the technology, and appropriate education and training RT3D echocardiography may evolve as a powerful supplement to conventional 2D echocardiography.

**Key Words**: Real time three dimensional, Fetal echocardiography, Live 3D, Two dimensional matrix transducer.

# **INTRODUCTION**

Congenital heart disease (CHD) continues to be a significant contributor to adverse perinatal outcomes and its prenatal recognition significantly improves the perinatal outcome [1]. Prenatal diagnosis of CHD has been possible only because of the advances in fetal echocardiography over the last three decades (Table **1**). Recent advances in three dimensional (3D) ultrasound imaging represent one of the most important technological innovations in this field. Even in 2D echocardiography, the operator conceptually recreates the spatial 3D reality of the fetal heart out of the 2D sonographic images. Although the current approach continues to function well, the advantages of 3D imaging are potentially significant revealing anatomical and functional complexities of the heart.

Currently there are two approaches to 3D sonography: (a) real time 3D (RT3D) echocardiography which generates and displays 3D images in real time, and (b) reconstructed 3D echocardiography which displays 3D images synthesized from sequential 2D images [2]. Real time 3D echocardiography is also known as live 3D echocardiography. The term four dimensional echocardiography is used to denote 3D images in motion, time being the fourth dimension. However, this may not distinguish between real time and reconstructed images. The technology of real time 3D echocardiography is still evolving and this review critically appraises this emerging technology in relation to fetal applications. The use of real time 3D in adult cardiac imaging [3] and in fetal cardiac assessment have been reported [4].

**Table 1:** Developmental History of Fetal Echocardiography

**\*Address correspondence to Dev Maulik MD:** Department of Obstetrics and Gynecology, University of Missouri Kansas City School Medicine, 2411 Holmes Street Kansas City, MO 64108-2792 USA Email<EMAIL_ADDRESS>
The innovation of 3D medical imaging can be traced to computed tomography (CT] and magnetic resonance imaging (MRI] technologies and essentially where the 2D tomographic image slices generated by these modalities are digitally reconstructed to produce 3D images. These developments have revolutionized medical imaging and diagnostics. However, even with the continuing advances in technology, CT and MRI are not useful for diagnostic imaging of the fetal heart.

Over the past decades, pioneering investigators utilized various experimental approaches involving offline reconstruction of 2D images [5-7]. The mode of image acquisition required locating the position of the transducer so that images could be collated in 3D spatial orientation. The method of tracking the transducer location included mechanical acoustic and magnetic devices. One of the most frequently utilized techniques in adult echocardiography employed a rotational transesophageal transducer with reconstruction of the 3D images with on or offline computers. However, these 3D methods could not perform in real time because of technological limitations.

Similar technical solutions evolved for creating of 3D echocardiographic images in the fetus [8, 9]. These approaches were based on postimaging reconstruction of fetal cardiac anatomy out of stored scanned volume data acquired by automatic or freehand techniques. These techniques produced fetal cardiac images that were not amenable to any useful interpretation because of the image quality and a lack of coherence between cardiac anatomical imaging and cardiac activity. These limitations, however, were substantially rectified through the innovation of gating techniques such as spatio-temporal image correlation (STIC) combined with a motorized rotating transducer head [10]. The method was innovated in Kretztechnik of Austria which is now a subsidiary of GE Healthcare. This approach is currently available in various ultrasound devices and is used to produce surface rendered images of the fetus (Figure ). There are numerous reports on fetal echocardiography using reconstructed approach with STIC. However, this approach does not offer true real time 3D cardiac imaging and has several limitations including high susceptibility to motion artifacts.

Two dimensional phased array technology for true RT3D ultrasound imaging was developed at the Duke University by von Ramm and associates [11]. Apparently the idea was first conceived for potential use as a sonar camera for underwater search and rescue. Because of its diagnostic potentials, the concept led to the development of medical imaging transducers with 2D array of numerous piezoelectric elements. and sparse phased array technology. In this array system, only a limited set of the elements of the array are used for transmission and reception of echoes. The image resolution of the sparse array technology was not adequate and the device as produced commercially (Volumetrics Ultrasound, North Carolina, USA) was not widely used. The next significant advances occurred in the Andover facility of the Agilent Technologies Healthcare Solutions Group, now a part of the Philips Medical System (Andover, Massachusetts, US) leading to the development of second generation two dimensional phased array technology. More recently, Siemens has also developed its own brand of real time 3D imaging technology. However, this is not available for fetal application at the time of writing this review.

The developmental milestones of 3D echocardiography of the fetus are summarized in Table **2**.

**Table 2:** Developmental History of Three Dimensional Fetal Echocardiography

# **BASIC PRINCIPLES OF REAL TIME THREE DIMENSIONAL SONOGRAPHY**

There are three fundamental steps of 3D sonography: (a) image acquisition, (b) image processing and (c) image display. These steps are sequential. Contemporaneous implementation of these processes during scanning constitutes RT3D ultrasound (Fig. **1**).

#### **IMAGE ACQUISITION AND PROCESSING**

#### **Two Dimensional Matrix Transducer**

The 2D matrix transducer is a phased array device comprised of approximately two to three thousand piezoelectric elements distributed in a two dimensional matrix array. All the elements transmit and receive unlike the sparse array system. The system steers the acoustic beam both in the azimuth and elevation producing a 3D pyramidal volume image data set in real time. The enormous volume of data thus generated offer a formidable challenge for real time processing. However, this issue was resolved by organizing the elements in groups known as subarrays with each subarray having its own beamformer. The subarray beam forming provides front end processing of the ultrasound signals, reduces the enormous computing burden, and facilitates RT3D image generation and display. Multiple miniaturized computer processor boards embedded inside the transducer handle perform this task.

#### **Image Data Processing**

The 3D image data are then transmitted to the ultrasound device's main computer system which handles simultaneously multiple streams of digital image data. Utilizing advanced data processing, the system generates a three dimensional pyramid shaped digital image data set (Fig. **1**).

**Figure 1:** Real time 3D image data set is displayed. The upper end of the pyramid indicates the two dimensional transducer footprint (arrow).

No gating is needed for this acquisition. This is known as the live 3D volume acquisition. A wider pyramidal volume known as the full volume measuring can also be imaged by swift automatic real time acquisition and integration of subvolumes. Generation of the full volume, however, requires some form of cardiac gating. In the adult or pediatric patient this is provided by the electrocardiogram of the patient. Obviously this is not feasible in the fetus. We have successfully simulated cardiac gating with an external electronic pulse generator trigger enabling us to acquire full volume data set of the fetal heart without any recognizable artifacts. The gating function is now integrated in the device.

#### **THREE DIMENSIONAL IMAGE DISPLAY AND ANALYSES**

The final critical component in 3D imaging is the analyses and display of the volume data set. This can be performed on the machine or offline using a proprietary software program (QLab, Philips Medical Systems) (Fig. **2**).

**Figure 2:** Real time 3D fetal echocardiography: A full volume 3D image data clip of the fetal heart and software image analysis tools are displayed in this illustration.

Three dimensional images can be displayed by (a) surface rendering with identification of various structures, or (b) volume rendering which creates a texture mapped block such as a pyramidal 3D object which can be rotated and cropped to reveal internal structures or flow (Fig. **3**).

**Figure 3:** Live 3D echocardiogram showing a four chamber view of the fetal heart. Fine line box depicts 3D orientation of the image data. The electrocardiogram in the lower part of the figure is actually simulated fetal heart tracing.

In addition to the structural evaluation, assessment of several cardiac functional parameters such as the ventricular volume and the ejection fraction can be determined. The software also allows optimization of the image attributes such as brightness and contrast. Fetal applications of these echocardiographic techniques are further discussed below.

The 3D image processing and display require defining the spatial location of a point in 3D space from the image data. The unit of 3D spatial graphic information is known as a voxel. The term stands for volume pixel and constitutes the smallest definable unit of a 3D image. A voxel is the 3D counterpart of a pixel which defines location in a 2D plane. Geometrically, the relative spatial locations of a voxel are represented by the Cartesian coordinates x, y and z (Fig. **4**).

**Figure 4:** Graphic illustration of the concept of a voxel which forms the units of the 3D image data. X, Y and Z represents the orthogonal coordinates (Cartesian) for the 3D space.

The location is defined by the point's distances from three orthogonal planes determined by these coordinates. This is a fundamental concept for 3D image processing and interpretation. Each voxel can be digitally quantified to represent objective properties such as opacity, density, color, velocity, or even time.

# **VOLUME RENDERED VIEWS**

The volume rendered moving image clips are reanalyzed with the software. This includes cropping image volume along the Cartesian orthogonal co-ordinates, X, Y, Z (Fig. **5**). Additional intracardiac anatomical views can be revealed by rotating the cropped 3D volume. Cropping can also be performed in variable inclined or oblique planes also known as adjustable planes.

**Figure 5:** Real time 3D fetal echocardiography. Fetal cardiac 3D image volume data is shown with the orthogonal (line box around the volume) and adjustable (green panel) cropping planes.

This technique permits a systematic examination of the cardiac chambers, the atrioventricular connections, the mitral and tricuspid valves, the interventricular and interatrial septa, and the outflow tracts and their interrelationship (Fig. **6**).

**Figure 6:** Real time 3D fetal echocardiogram showing cardiac structures following cropping in two orthogonal planes and rotating the image data set.

Moreover, it enables visualization of surface or "en face" views of intracardiac structures. Such anatomical views and details could be of great value for prenatal diagnosis and prognostication.

# **TWO DIMENSIONAL VIEWS OF THREE DIMENSIONAL IMAGE DATA: MULTIPLANAR AND TOMOGRAPHIC VIEWS**

Multiplanar viewing using orthogonal and inclined planes can also performed revealing display of 2D cardiac images in three separate planes simultaneously (Fig. **7**).

**Figure 7:** Real time 3D fetal echocardiography. The left panel shows the 3D image data volume and the software analytic tools. The right panel shows multiplanar views of the fetal heart. The lower right subpanel shows the image planes (MPR) of the other three 2D cardiac images.

Similarly, tomographic 2D image slices of the heart can be generated with control over the region of interest, the number of slices and the thickness of a slice (Fig. **8**)

**Figure 8:** Real time 3D fetal echocardiogram showing the tomographic slicing of the 3D cardiac image volume (upper right panel). The lower most right panels show the orientation, thickness and number of image slices.

#### **THREE DIMENSIONAL REAL TIME COLOR DOPPLER ECHOCARDIOGRAPHY**

Three dimensional color Doppler imaging of the intracardiac flow can be acquired with 2D matrix array technology (Fig. **9**). However, the inherent limitations of Doppler sonography such as angle dependence are also applicable in these modalities.

**Figure 9:** Real time 3D color Doppler fetal echocardiogram showing atrioventricular flow. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle; MV = mitral valve; TV = tricuspid valve; IAS = interatrial septum; IVS = interventricular septum; S = ventricular septum

Three dimensional color Doppler flow depiction can be used to quantify abnormal flow conditions such as regurgitant jets and turbulent flow (Fig. **10**). Potential also exists to quantify volumetric flow using this approach.

**Figure 10:** Live 3D echocardiography in 36 week old fetus with complete atrioventricular septal defect. Four chamber views cropped to show the abnormal atrioventricular hemodynamics. (Modified with permission from reference 4)

#### **FUNCTIONAL ASSESSMENT OF THE HEART**

An additional innovative aspect of the image analytic software is the ability to perform dynamic cardiac quantification such as the ventricular volume through the cardiac cycle and the ejection fraction. The distinct advantage of RT3D approach over traditional echocardiography is that it is not subject to assumptions regarding the volume and the shape. The current RT3D technology allows fast creation of a full 3D wire-mesh endocardial volume that is sensitive to the annulus and apex motions. Detailed analysis of the left regional and global ventricular function can be performed using RT3D technology.

### **FETAL APPLICATION OF RT3D ECHOCARDIOGRAPHY**

The feasibility of using RT3D fetal echocardiography was demonstrated by Maulik and colleagues in 2003. The study demonstrated the unique capabilities of the technique in clarifying the complex structural and hemodynamic abnormalities of congenital heart defects of the fetus. Specifically, the en face views of cardiac lesions such as common atrio-ventricular valves or a ventricular septal defect provide anatomical perspectives beyond the scope of the existing two dimensional echocardiography technology (Figs. **11, 12** and **13**) [4].

**Figure 11:** Live 3D echocardiography in 36 week old fetus with complete atrioventricular septal defect. Four chamber views cropped to show the common atrioventricular valve (v) and the defect (asterisk). (Modified with permission from reference 4)

**Figure 12:** Live 3D echocardiography in 36 week old fetus with complete atrioventricular septal defect. The pyramidal section has been cropped from the top and rotated toward the examinerto di0play all five leaflets of the common atrioventricular valve (V); posterior (P), left lateral (L1), left anterior (A1), right anterior (A2), and right lateral (L2). Small portion of the ventricular septum (S) and atrial septum (AS) have been retained to show their relationship to V. V is open in A and closed in B (Modified with permission from reference 4)

**Figure 13:** Live 3D echocardiography in 36 week old fetus with complete atrioventricular septal defect. En face viewing of the defect (asterisk) from the inferior aspect. (Modified with permission from reference 4)

Subsequent publications have further confirmed this [12]. Acar and colleagues used RT3D echocardiography using the matrix probe in 60 fetuses 16 of whom had congenital cardiac defects or myocardial dysfunction. The procedure was successful in 93%. The investigators found the technique helpful allowing a multiplanar and novel inside 3D views of the fetal heart. Chen and co-workers compared diagnostic efficacy of RT3D echocardiography with 2D echocardiography in 30 patients with complex defects. [13]. Receiver operating characteristic (ROC) analysis showed that when in predicting the surgical findings, RT3D echocardiography was correct in 75.6% and 2D echocardiography was correct in 64.4% of the cases.

#### **CHALLENGES FOR REAL TIME 3D ECHOCARDIOGRAPHY OF THE FETUS**

The major challenge for the current stage of the technology is the natural resistance to adopting apparently complex new technology. This is partly related to the fact the value of real time 3D echocardiography in prenatal diagnosis of complex cardiac defects remains underestimated. There are also technological issues related to fetal application of the technology. This technology is developed primarily for adult and pediatric cardiac diagnosis and therefore is not optimized for fetal application. Specifically the currently available 3 Mz adult transducer may not provide optimal resolution for prenatal diagnosis. The current 7 MHz pediatric transducer provides significantly improved image resolution but may not always provide enough depth penetration. The newer generation transducers with pure crystal technology may improve this situation.

The software tools for image analysis are highly sophisticated but may offer a steep learning curve for many. A recent study demonstrated the benefits of intensive education and training on the diagnostic efficacy. Jenkins and associates [14] investigated the impact of an intensive interactive training course on the efficacy of RT3D echocardiography in adult patients and found that training significantly improved the correct diagnosis rate of the new technique. However, there was no additional value of the technique over traditional 2D technology without such training although most participants had access to the RT3D method. This would be even more relevant for fetal application of the technology. Emergence of automation in image analysis may also significantly enhance its adoption for the main stream practice. Finally there is a great need for further research and education in this field.

#### **REFERENCE**

© 2010 The Author(s). Published by Bentham Science Publisher. This is an open access chapter published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

# **Rendering Cardiac Volumes in Three and Four-Dimensional Ultrasonography**

# **Jimmy Espinoza\***

*Department of Obstetrics and Gynecology, William Beaumont Hospital Royal Oak, MI USA*

**Abstract**: This chapter summarizes different approaches currently used to examine the fetal heart using three and four-dimensional ultrasonography with a particular emphasis on multiplanar display and novel rendering modalities. These new imaging modalities provide important insight into the normal and abnormal fetal cardiac anatomy and function and have the potential to reduce the operator dependency that characterizes twodimensional ultrasound.

**Key Words**: Fetal Echocardiography, 4D Fetal Echocardiography, Volume Rendering.

#### **INTRODUCTION**

A growing body of evidence indicates that four-dimensional (4D) ultrasound imaging with spatiotemporal image correlation (STIC) facilitates examination of the fetal heart [1-45]. Thus, 4D fetal echocardiography have the potential to reduce the operator dependency that characterize two-dimensional ultrasonography and may increase the detection rate of congenital heart defects (CHDs). Volume datasets obtained with 4D sonography can be compared with blocks of pathological specimens, where all the anatomical information is contained in the block and the information displayed depends on the level at which the block is cut, with the additional advantages that these planes can be assessed in a virtual beating heart and that rendering techniques can be used to gain additional insight into the structure and function of the fetal heart. Prenatal diagnosis of congenital heart defects is challenging because of the structural complexity of the heart and the expertise required to master the use of standard planes for fetal echocardiography. In addition fetal and/or maternal motion, maternal body mass index, gestational age, adequacy of the amniotic fluid volume and fetal position are important factors that can affect image quality. Prenatal diagnosis of CHDs is desirable because unrecognized congenital heart defects may be associated with worse neonatal outcome. 4D ultrasonography with spatiotemporal image correlation (STIC) allows the acquisition and storage of volume data sets of the fetal heart using which can be resliced to obtain the standard planes for fetal echocardiography, as well as novel planes. In addition to this anatomic information, functional information of the fetal heart can also be obtained including the direction of blood flow if the volume dataset was obtained color Doppler or high dimensional (HD) power Doppler

The image quality contained in a STIC volume dataset can be substantially improved by optimizing the settings before acquisition. This can be achieved by adjusting the two-dimensional grayscale and color Doppler parameters. Our preference is to use low persistence, high contrast, and high frame rate settings. Typical acquisition time ranges from 5 to 15 seconds. Shorter acquisition times can be used to minimize motion artifacts but this reduces the image spatial resolution. At the time of volume acquisition, transverse sweeps of the fetal thorax can yield better images of four-chamber, five-chamber, and three-vessel and trachea views. In contrast, sagittal sweeps through the fetal thorax can yield better images of the aortic and ductal arches as well as the venous connections to the fetal heart

#### **Evaluation of the Fetal Heart Using 3D and 4D Ultrasonography**

Two-dimensional (2D) ultrasonography relies on standard anatomic planes for the examination of the fetal heart, including the four-chamber view, three-vessel and trachea view, the left and right outflow tracts [46-51]. However, visualization of vascular connections to the fetal heart with two-dimensional (2D) ultrasonography requires the examiner to scan these vascular structures in multiple scanning planes to obtain a mental reconstruction of their spatial relationships. This process can be facilitated using different display modalities used in 3D and 4D ultrasonography including power Doppler reconstruction 3D and 4D volume datasets, [52-56] minimum projection mode, [39] inversion mode, [40, 42, 57] and B-flow. [58-60]

**<sup>\*</sup>Address correspondence to Jimmy Espinoza MD:** Department of Obstetrics and Gynecology William Beaumont Hospital Royal Oak, MI USA; E-mail<EMAIL_ADDRESS>
#### **Multiplanar Display**

Multiplanar display is a unique modality available in 3D and 4D ultrasonography that allows for the simultaneous visualization of three anatomic planes which are orthogonal to each other: the transverse, sagittal and coronal planes (Fig. **1**).

**Figure 1:** Volume datasets were adjusted to display the four chamber view in panel A, where the fetal aorta was aligned with the crux of the heart in the vertical plane. The reference dot was positioned in the aorta allowing the visualization of the coronal view of the descending aorta in panel C.

Moreover, an imaging tool referred as the reference dot allows for the identification of anatomic structures in these three orthogonal planes. This display modality can also be used to scroll through the volume data set to visualize the transverse view of the upper abdomen, four-chamber view, five-chamber view and the three-vessel view.

A central feature of this display modality is the ability to focus on a specific anatomic structure in panel A by placing the reference dot in the structure and visualizing the same structure in two perpendicular planes displayed in panels B and C (Fig. **1**). Using this approach we demonstrated that the simultaneous display of orthogonal planes of abnormal vascular connections to the fetal heart facilitated the identification of the nature of the abnormal vessel and the visualization of its spatial relationships with other vascular structures. Indeed, the multiplanar view allowed for the visualization of the drainage of a dilated azygos/vein into the SVC (Fig. **2**) in a fetus with interrupted IVC with hemiazygos vein continuation.

This technique involves the visualization of standard views used in fetal echocardiography in panel A and the subsequent placement of the reference dot in the abnormal vascular structure to identify the nature of the vessel and its connections which where displayed using the sagittal and coronal planes in panels B and C, respectively. This technique can be improved by adding the spin technique [61] (see below).

**Figure 2:** Multiplanar display of a dilated hemiazygos vein in a fetus with interrupted inferior vena cava and dextrocardia. The reference dot was placed in the dilated hemiazygos vein in the four chamber view of the heart in panel A. This allowed for both the visualization of the sagittal view of the hemiazygos vein in panel B and the coronal view of the dilated hemiazygos vein in panel C. The rotation of the coronal view to a vertical position on panel C allowed for the visualization of the dilated hemiazygos vein draining into the SVC. SVC: superior vena cava; RA: right atrium

#### **40** *Four Dimensional Fetal Echocardiography Jimmy Espinoza*

Several algorithms using the multiplanar display have been proposed for simultaneous display of both outflow tracts [25], to visualize the aortic and ductal arches [62], (Video 1) and to determine the nature of vascular connections to the fetal heart using the spin technique [38]. The later involves positioning the reference dot in the center of the structure and 'spinning ' the volume data set around the *y* axis to determine its spatial relationship with the heart and other vascular structures and to identify its nature

A detailed examination of the fetal heart has been proposed to include a long-axis view of the arterial duct [51] (sagittal view of the ductal arch). This sonographic plane allows visualization of the right ventricle in continuity with the main pulmonary artery, pulmonary valve, ductus arteriosus, and descending aorta, as well as a transverse view of the ascending aorta (Fig. **3**).

**Figure 3:** The components of the sagittal view of the ductal arch (Fig. **1a**) as determined by the multiplanar display are displayed in Fig. **1b**, including: right ventricular outlet (RV), main pulmonary artery (PA), ductus arteriosus (DA), descending aorta (DAo), and a cross-section of the ascending aorta (AAo).

The sagittal view of the ductal arch can be easily obtained using 4D volume datasets of the fetal heart acquired with STIC by following the first two steps of a reported algorithm [63]. Briefly:

**Figure 4:** In panel C, the image was rotated to display the aorta in a vertical position, when necessary. This allowed for the visualization of the longitudinal view of the ductal arch in panel B.

Video 2 illustrates the simplicity of these steps. A retrospective study using this approach [63] reported that the visualization rate of the sagittal view of the ductal arch was significantly lower in fetuses with conotruncal anomalies 5.6% (1/18), than among normal fetuses [93.1% (108/116)] and those with other CHDs [79.4% (27/34); p<0.01]. The authors concluded that the inability to visualize the ductal arch using the proposed algorithm should raise the possibility of conotruncal anomalies because it is associated with a nine-fold increase in the risk for a conotruncal anomaly [64]. However, prospective studies are required to determine the value of the proposed approach in the screening for conotruncal anomalies

Rendering techniques can also be applied to the visualization of vascular connections to the fetal heart to obtain a depth perspective using a "thick slice".64 (Fig. **5**)

**Figure 5:** "thick slice" rendering of an aortic arch in a patient with aortic coarctation. Contraductal shelf (CS), descending aorta (D Ao), inferior vena cava (IVC), left ventricle (LV), left atrium (LA), ascending aorta (A Ao), left subclavian artery (LSA)

## **Automated Display of Multiple Slices**

Several ultrasound manufacturers provide software to automatically slice 3D and 4D volume data sets (Multislice View ™ ; Accuvix, Medison, Seoul, Korea; Tomographic Ultrasound Imaging; GE Healthcare, Milwaukee, WI; iSlice; Philips Medical Systems, Bothell, WA; Multi-Slice View; Siemens Medical Solutions, Malvern, PA). This technology allows an examiner to automatically display several slices that are parallel to each other on a single screen

TUI has been introduced as a new display technology for 3DUS and 4DUS. This modality allows for the simultaneous display of up to eight parallel planes whose distance can be adjusted for a better visualization of anatomic planes. Thus, TUI allows the visualization of multiple sections of a beating heart at the same time. An "overview image" is shown on the upper left corner. This view shows a plane orthogonal to the slices, and parallel lines demarcate the position of the slices within the volume dataset (Fig. **6**).

**Figure 6:** An "overview image" is shown on the upper left corner. The parallel lines determine the position of the eight orthogonal planes to the plane containing the "overview image"

The user can adjust the number and position of the slices with specific software controls. TUI has been used for the examination of the fetal heart [65-68]. and other fetal organs [69]. However, the simple use of parallel planes to the four-chamber view of the heart does not allow for the visualization of the long axis view of the left outflow tract and the short axis view of the aorta, which are considered part of an integral examination of the fetal heart [49-51, 70].

#### **42** *Four Dimensional Fetal Echocardiography Jimmy Espinoza*

Moreover, the untargeted use of TUI allows for the simultaneous display of anatomic planes with and without diagnostic value. In order to determine the minimum number of images required for a comprehensive examination of the fetal heart we developed an algorithm using TUI and STIC [71]. This algorithm allows for the simultaneous visualization of the standard planes for fetal echocardiography including the four-chamber view, three-vessel view, left outflow tract and short axis (right outflow tract), in most fetuses without CHDs [71]. With the use of this algorithm a normal four-chamber view, five-chamber view, longitudinal view of the ductal arch, three-vessel and trachea view, left outflow tract and short axis were visualized in 99%, 96.9% , 98.5 % , 88.2%, 93.3%, and 87.2% of the volume datasets, respectively.

Similar results were recently reported by Rizzo et al [72]. using STIC and a simplified method referred to as the "three-steps technique."

The former algorithm involves the steps that are displayed in Video 3 and include:

Step 1: Placement of the reference dot in the crux of the heart and alignment of the aorta in the midline on panel A (Fig. **7**)

**Figure 7:** Volume datasets were adjusted to display the four chamber view in panel A, where the fetal aorta was aligned with the crux of the heart in the vertical plane. RV: right ventricle; LV: left ventricle; Ao: aorta

Step 2: Placement of the reference dot on the aorta in panel A to visualize the coronal view of the aorta in Panel C (Fig. **8**)

**Figure 8:** The reference dot was positioned on the aorta in panel A allowing the visualization of the coronal view of the descending aorta in panel C.

Step 3: On panel C, rotate the aorta until it is in a vertical position. This allows the visualization of the sagittal view of the ductal arch in panel B (Fig. **9**)

**Figure 9:** In panel C the image was rotated to display the aorta in a vertical position. This allowed for the visualization

Step 4: Move the reference dot back to crux of the heart in panel A, in preparation for TUI activation

Step 5: Activate Tomographic Ultrasound Imaging

Step 6: Reduce the number of slices to 3 and change the display format to four planes. This will automatically enlarge the images displayed (Fig. **10**)

**Fig 10**: see text

Step 7: Right click on panel A and move the image to place reference dot in the aorta. This step allowed the visualization of the five-chamber view on panel C which corresponds to the slice marked with an asterisk in the "overview image" (Fig. **11**)

#### **44** *Four Dimensional Fetal Echocardiography Jimmy Espinoza*

Step 8: Click on the "adjust" option and right click on panel B to display a horizontal arrow. Move this arrow to the left until the upper line (-1) on panel A coincides with the ductal arch. (Fig. **11**)

Step 9: Right click on panel D to display the horizontal arrow. Move this arrow to the left until the lower line (1) on panel A coincides with the edge of the aorta. This allowed the visualization of the four-chamber view on panel D in 99% (193/195) of fetuses without heart defects (Fig. **11**)

Step 10: Left click on panel C and on "Rotation Y". Scroll the bar on the "Rotation Y" to the right until the left outflow tract is visualized on panel C. This is generally accomplished with a right sided rotation between 8 to 22 degrees depending on the gestational age at which the volume dataset was obtained. This step allows the visualization of the left outflow tract in panel C and the short axis of the aorta in panel A. In about one third of fetuses the reference dot in panel C need to be placed above the aortic valve to visualize the short axis of the aorta in panel A. (Fig. **12**)

**Figure 12**: see text

#### **Rendering Techniques**

Several rendering algorithms have been described for visualization of the three-dimensional structure and spatial relationships of great vessels and venous return to the heart. These images can be obtained by acquiring volume data sets with gray-scale, color Doppler, power Doppler or B-flow imaging

# **Inversion Mode**

The "inversion mode" is a new rendering algorithm that transforms echolucent structures into solid vowels. Thus, anechoic structures such as the heart chambers, lumen of the great vessels, stomach and bladder appear echogenic on the rendered image, whereas structures that are normally echogenic prior to gray-scale inversion become anechoic. Post processing adjustments are performed as necessary, including adjustments of the gamma curve, threshold and transparency to improve image quality. The technique allows examiners to obtain 4D rendered images of cardiovascular structures from volume data sets acquired with gray-scale only, without the need for color Doppler, power Doppler, or B-flow imaging. We have previously demonstrated the value of the display technique in the visualization of dilated azygos or hemiazygos veins and their spatial relationships with the descending aorta, the aortic arch, the SVC, the right atrium, and the fetal spine in cases of interrupted IVC associated with and without heterodoxy syndromes (Fig. **13**).

As mentioned above, volume datasets obtained with a sagittal sweep of the fetal chest are preferred over those obtained using a transverse sweep when evaluating the normal or abnormal vascular connection to the fetal heart. Once a sagittal view of the heart is visualized in Panel A, the region of interest was selected in panel B, reducing the rendering box height and width to display only the fetal spine, fetal heart and its vascular connections. Next the direction of view (green dotted line) was set to display the sagittal view of the heart in the anteroposterior projection and finally the "inversion mode" rendering algorithm was selected in the ultrasound equipment with the threshold filter set between 70 and 90.

**Figure 13:** Three-dimensional images of a fetal heart rendered with the "inversion mode" in case of interrupted IVC with azygos vein continuation. RA: right atrium; SVC: superior vena cava. A posterior view of the fetal heart shows a dilated azygos vein located to the right of the descending aorta. The arch of this vein forms a Y image with the aortic arch before joining the SVC

#### **Transparence Modes**

The minimum projection mode (MPM) is another volume-rendering tool that allows preferential display of minimum gray values within a volume dataset. This algorithm can be useful for displaying vascular structures and fluid-filled organs [73-74]. The MPM can provide important insight into the spatial relationships of abnormal vascular connections to the fetal heart in the upper mediastinum and could potentially be useful in the determination of atria morphology in cases of left and right isomerism.39 (Fig. **14**)

**Figure 14:** Comparison of minimum projection mode (MPM) images, on the right, with their corresponding two-dimensional images, on the left, in a case of left isomerism with interrupted IVC and azygos continuation. A) The four-chamber view shows a two-vessel sign; the MPM image shows that both atria appendages (APP) are morphologically left; B) Three-vessel view. In the MPM image, the azygos vein drains into the superior vena cava (SVC) and the right atrium, whereas the two-dimensional ultrasound image shows only the ascending aorta, the pulmonary artery and the dilated right atrium. RA: right atrium, RV: right ventricle; LV: left ventricle; LA left atrium, Ao: aorta; AZ: Azygos vein; PA: pulmonary artery; Ao Arch: aortic arch, T: trachea, \*: Azygos' arch

#### **B-flow**

B-flow is a new display modality in 4D ultrasound that digitally enhances signals from weak blood reflectors from vessels and, at the same time, suppresses strong signals from surrounding tissues [75-77]. Because this technology does not rely on Doppler methods to display blood flow, it is angle-independent and does not interfere with the frame rate. This is potentially advantageous over color or power Doppler imaging when used in conjunction with

#### **46** *Four Dimensional Fetal Echocardiography Jimmy Espinoza*

STIC for the evaluation of the fetal vasculature. In B-flow imaging the echoes from the tissue and that of the blood flow can be displayed with high resolution and without the overlay that characterizes color Doppler imaging. Moreover, B-flow may have less signal drop out when the ultrasound beam is perpendicular to the vessel. The use of B-flow in the case presented herein demonstrates that this imaging modality provides important insight into the location and nature of arch abnormalities in fetuses with coarctation of aorta. Indeed, B-flow allowed for a clear visualization of a thin and tortuous aortic arch as well as its spatial relationships with the fetal heart and other vascular structures (Fig **15**).

**Figure 15:** B-flow imaging of a narrow and tortuous aortic arch aortic arch and its relationship with the heart and other vascular structures: aortic arch (Ao A), descending aorta (Dao), ductus venosus (DV), inferior vena cava (IVC), umbilical artery (UA)

#### **REFERENCES**

© 2010 The Author(s). Published by Bentham Science Publisher. This is an open access chapter published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode

# **Analysis of Acquired Volumes: Methodological Approach**

# **Greggory R DeVore**

#### Fetal Diagnostic Center Pasadena, CA, USA

**Abstract**: The purpose of this paper is to review how 3D/4D echocardiographic images can be manipulated to maximize the information regarding cardiac structure to improve the diagnostic yield of congenital heart defects. The following topics are discussed: (1) the differences between 3D and 4D ultrasound; (2) basic imaging principles of fourdimensional ultrasound when using spatial-temporal image correlation, real-time volume display, and matrix array technology; (3) analysis of acquired volumes using X,Y and Z rotation, the transverse sweep, the spin technique, tomographic imaging, rendering, inversion, and B-flow. The conclusion is that while the 3D and 4D volumes are easy to acquire, the user must understand the number of tools available to enhance the examination of the fetal heart.

**Key Words:** 4D ultrasound, Fetal echocardiography, Cardiac volumes, Methodology.

#### **INTRODUCTION**

Fetal echocardiography was introduced to clinical medicine in the early 1980's when the first studies reported its use for evaluation of cardiac arrhythmias as well as basic cardiac anatomy using M-mode, M-Mode-directed real-time, and real-time ultrasound [1-21]. In the late 1980's color and pulsed Doppler ultrasound were added to the armamentarium so that blood flow could be evaluated. [22-29]. These diagnostic tools allowed the fetal examiner utilize tools that were the standard for pediatric and adult echocardiography [30].

During the past seven years a new imaging modality, 3D/4D ultrasound, has emerged as an important adjunct to cardiac imaging [31-72]. This modality has allowed the examiner to review cardiac anatomical relationships in a manner that has not been available in the past. After acquiring 3D/4D fetal cardiac volume datasets the examiner must use sophisticated online and/or offline computer programs to analyze the fetal heart. For many physicians who are only familiar with acquiring and interpreting 2D images (B-mode, color Doppler, pulsed Doppler) the concept of manipulating a 3D/4D dataset may be a daunting task. The purpose of this paper is to review how 3D/4D echocardiographic images can be manipulated to maximize the information regarding cardiac structure for improved diagnostic yield. This paper will include a description of each technique, a cine clip illustrating the technique, a link to a free downloadable program used for volume manipulation, and sample volumes the user can download and evaluate.

#### **DIFFERENCES BETWEEN 3D AND 4D ULTRASOUND**

When three-dimensional (3D) ultrasound was introduced to the imaging community as a commercial product it consisted of multiple 2D images that were stacked one behind another during a manual or automated sweep of the transducer beam through an area of interest (Fig. **1**).

**Figure 1**: This illustrates the acquisition of multiple 2D images obtained during the sweep of the transducer beam through the **\*Address correspondence to Greggory R DeVore:** Feala Diagnostic Center Pasadena CA, USA; E-mail<EMAIL_ADDRESS>
fetal chest.  This technique is used with mechanical transducers in non-pediatric 3D and 4D ultrasound machines.

Imaging of the heart proceeded without regard to changes in diastolic and systolic cardiac configuration that occur during the cardiac cycle. The ''non-gated'' approach to reconstructive 3D imaging results in a ''static'' image display of non-cardiovascular and cardiovascular anatomy that can be examined simultaneously in three planes (X, Y and Z) that are perpendicular to each other (Fig. **2**).

**Figure 2:** Following the acquisition of sequential, parallel 2D images, the volume dataset is created containing voxels. Each voxel consist of a volume of image pixels that have an X, Y, and Z component. The X plane image is obtained during the initial acquisition and has the characteristics of axial (A) and lateral (L) resolution of the 2D image which is a function of the characteristics of the transducer beam. The Y and Z planes also have axial and lateral resolution. However, the resolution in these planes is a function of the transducer beam as well as the size of the voxel that is created from the original volume dataset. For this reason, the Y and Z images are of lower resolution than the image in the X plane.

The X plane image has the highest resolution and is equivalent to the 2D image displayed during the 3D volume acquisition (Fig. **2**). The X plane image consists of pixels that have the properties of axial and lateral resolution, identical to a typical 2D image. Axial resolution provides the greatest detail for imaging tissue structures in the plane of the ultrasound beam, while lateral resolution provides less detail because it displays structures lateral to the ultrasound beam (Fig. **2**). Therefore, the X plane image would be equivalent to a 2D image displayed during a non-3D examination of the fetus. As the two-dimensional images acquired during the 3D volume acquisition are stacked one behind another, a voxel is created which has X, Y, and Z components (Fig. **2**). The size of the voxel determines the resolution of the images in the Y and Z planes (Fig. **2**). The 3D Y plane displays an image perpendicular to the X plane, in a vertical orientation (Fig. **2**). This image has less detail than the X plane image because it is reconstructed from voxels within the volume dataset. Although the Y plane image has less detail than the X plane image, it has more detail than the Z plane image. The Z plane image is perpendicular and horizontal to the X plane (Fig. **2**).

While the ability to examine cardiac structures in three perpendicular planes is a new approach not available with conventional 2D imaging, there are two limitations when comparing this to a 2D real-time image display of the fetal heart. The first is that the image is ''static'', thus not displaying a real-time image of cardiac structures, i.e. wall motion and opening and closing of valves. This would be equivalent to a freeze frame image obtained by pausing a video tape player, or freezing a still image while performing a live 2D real-time examination. The second limitation is the speed at which the volume dataset is acquired. All 3D ultrasound machines allow the examiner to control the sweep speed during image acquisition. The slower the sweep speed, the higher the resolution of the images displayed in the Y and Z planes. However, at slower sweep speeds artifact is introduced in the Y and Z planes as the result of fetal somatic and cardiac motion (Fig. **3**), thus negating the benefit of the 3D volume dataset. Conversely, the faster the sweep speed the lower the resolution in the Y and Z planes. However, with a faster sweep speed there is less of a chance of artifact introduced from cardiac motion (Fig. **3**).

**Figure 3:** This is a static 3D sweep through the fetal chest containing cardiac structures. This image acquisition was sagittal, from left to right. The Y plane illustrates the reconstructed four-chamber view of the heart. The upper panel demonstrates the X and Y planes in which the sweep speed is set at a slow rate to acquire a greater number of 2D images to construct the 3D dataset. Using this technique increases the image resolution in the X plane. However, because of the decreased sweep speed, there is artifact in the Y plane resulting from contraction of the fetal heart during the image acquisition. The lower panel demonstrates a similar sweep at a lower speed. The Y plane does not demonstrate artifact, however, the image resolution of the four-chamber view is less.

Because the 3D static sweep captures cardiac structures randomly within the cardiac cycle, measurements of chamber and outflow tract dimensions at end-diastole or end-systole cannot be made. Therefore, when the examiner acquires a 3D static volume dataset of the fetal heart it is desirable to determine the transducer sweep speed that optimizes image resolution without introducing movement artifact in the Y and Z planes.

#### **Basic Imaging Principles of Four-Dimensional Ultrasound**

The question often asked is "what is four-dimensional (4D) ultrasound?" The fourth dimension is time, i.e. rapidly displaying 3D datasets so that the structures displayed on the screen appear to be moving. This gives the impression of motion such as a smiling face, movement of extremities, and contraction of the heart. This is similar to real-time ultrasound in which static 2D images are displayed on the screen at a rapid rate (frequency) giving the illusion of movement. Currently, there are several 4D technologies that are commercially available that will be discussed in this section.

### *Mechanical Array Transducer*

#### **Spatial–Temporal Image Correlation (STIC)**

Initially the reconstruction of image datasets was time consuming and could only be performed with computerized offline data analysis and rendering. This prevented the clinical use of this technology on a widespread basis. In 2002 GE-Kretz (Voluson 730 Expert, Zipf, Austria) introduced the first clinical ultrasound machine that reconstructed 3 dimensional datasets of the fetal heart and displayed a cine loop of a single cardiac cycle [48]. The technology that was used is called spatial–temporal image correlation (STIC). After the introduction of B-mode STIC in 2002, STIC color and power Doppler were introduced in 2003 [44]. Since the first introduction of STIC, additional manufacturers have introduced similar technologies. The STIC volume display consists of thousands of 2D images acquired through the area of interest during a single sweep that lasts between 7.5 and 15 seconds. The images are then analyzed and multiple volumes are correlated with end-systole and end-diastole to create a cine loop of a single cardiac cycle. This allows the examiner to evaluate the volume dataset, identical to what is accomplished with the 3D static volume, with the only difference being that cardiac structures are viewed as a cine loop of a single cardiac cycle. STIC technology can display the data as either a B-mode image, B-mode with color Doppler, B-mode with Power Doppler, color Doppler, power Doppler, and B-flow (Fig. **4**).

**Figure 4**: This is a STIC acquisition of the four-chamber view. The upper and lower panels are identical images, except for display of the color Doppler in the lower panel. The upper panel demonstrates the four-chamber view in the X plane and an "enface" view (outlined by black line) of the ventricular septum in the Y plane. Careful examination does not suggest any pathology of the interventricular septum. The lower panel, with color Doppler activated, demonstrates a shunting ventricular septal defect near the apex in the X plane. The size and location of the septal defect is clearly identified in the "enface" view of the Y plane.

The only limitation of the STIC volume data acquisition is that fetal movement may occur during the volume acquisition. Depending upon the type of movement (fetal breathing, gross body movement, maternal breathing) the images in the X, Y and Z planes may be minimally altered, or may become non-interpretable. Like the static 3D volume data acquisition, the resolution of the images in the X, Y, and Z planes are a function of how the user acquires the volume dataset. The volume sweep speed can be selected between 7.5 and 15 seconds and the angle of the sweep between 15 and 40 degrees. The angle of the sweep is equivalent to the distance covered during the sweep; a shorter distance is equivalent to a smaller angle; a larger distance is equivalent to a larger angle

For example, if the selected time is 7.5 seconds, a fixed number of images will be acquired whether the angle is 15 or 40 degrees. Therefore, the image resolution will be higher when the angle is 15 degrees than if it were 40 degrees. The reason for this is that although the same number of images are acquired during the 7.5 seconds, there is a greater distance between the images than when the angle is smaller. This results in lower resolution images in the Y and Z planes in the 40 degree sweep than in the 15 degree sweep. The advantages of STIC technology are the following: (1) looped cardiac cycle that simultaneously displays cardiac anatomy in the X, Y and Z planes (Fig. **5**),