Advanced cardiac imaging in the newborn: Tissue doppler imaging and speckle tracking echocardiography

Introduction

Myocardial performance plays an important role in determining short- and long-term outcomes in term and preterm infants. Echocardiography is the most commonly used diagnostic modality for cardiovascular assessment in neonates; however, measuring the nature of cardiac mechanics is difficult due to the complex myocardial geometry and the interplay of cardiac loading conditions. In neonates myocardial performance can be characterized by three separate echocardiography techniques: (1) changes in cavity dimensions, (2) displacement and velocity of a single point along the myocardial wall, and (3) deformation of a segment of the wall. Until recently, the use of echocardiography in neonates to assess the adequacy of the cardiovascular system was largely dependent on either a subjective assessment of myocardial function, the use of measurements of cavity change during the cardiac cycle (e.g., shortening fraction, SF, and ejection fraction, EF), or blood flow velocity. However, not all aspects of cardiac mechanics can be identified using conventional echocardiography techniques; specifically, it is difficult to capture either the twisting motion or wall thickening for the whole ventricle. Furthermore, wall motion measurements cannot differentiate between active and passive movement of a myocardial segment. For example, on conventional echocardiography, a myocardial segment that has lost its function may still show movement due to the tethering effect of adjacent segments leading to misdiagnosis. Two emerging and validated modalities that directly assess muscle wall characteristics in neonates, tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (2DSTE), enable acquisition of quantitative information that supersedes the qualitative impression provided by conventional methods.

TDI is a modality that captures information on muscle movement velocity and cardiac cycle event timings using a high temporal resolution. The Doppler effect is the term given to the change in frequency of a wave reflected by an acoustic source when there is relative movement between the source and the wave transmitter and can be applied in the assessment of heart muscle (tissue) characteristics. This was first demonstrated by Isaaz et al. in their assessment of the left ventricular (LV) wall using a pulse wave (pw) frequency signal. TDI captures information using high frame rates (typically greater than 200 frames per second). The high temporal resolution achieved using this technique facilitates the measurement of a wide array of myocardial muscle characteristics including the velocity of muscle movement during systole and diastole, deformation measurements (also known as strain and strain rate (SR) measurements), in addition to the measurements of the timing of events within the cardiac cycle (systolic and diastolic times/isovolumic contraction and relaxation times). Those measurements can now be derived by pw tissue Doppler imaging (pwTDI) and color TDI (cTDI) ( Figure 11.1 ).

Myocardial deformation analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular and atrial function in neonates. Cardiac strain is a measure of tissue deformation, and SR is the rate at which this deformation occurs. Myocardial strain can be measured in terms of three normal strains (longitudinal, radial strain, and circumferential) and six shear strains ( Figure 11.2 ). Currently, only normal strain and shear strain in the circumferential-longitudinal plane (rotational mechanics) have been investigated for clinical use in neonates. These measurements can be obtained in neonates using TDI or 2DSTE. ^{, ,} Characterization of cardiac performance with myocardial deformation by 2DSTE is a validated method to assess both ventricular contractility and loading conditions in term and preterm infants and provides fundamental information on myocardial properties and mechanics that would otherwise be unavailable with conventional imaging. ^, 2DSTE is a non-Doppler technique that applies computer software analysis of images generated by conventional ultrasound techniques. The Doppler ultrasound signal generates artifacts due to random reflections, called speckles. These speckles stay stable during the cardiac cycle and can act as natural acoustic markers. Speckle tracking software defines and follows clusters of speckles from frame to frame to calculate parameters of motion (displacement and velocity) and parameters of deformation (strain and SR). ^,

There is an expanding body of literature describing longitudinal reference ranges and maturational patterns of TDI velocity– and 2DSTE-derived strain values in term and preterm infants. ^{, ,} Comprehension of principles, technical aspects, and clinical applicability of each modality is a prerequisite for its routine clinical use in neonates. This chapter will introduce the reader to TDI and 2DSTE of the LV and right ventricle (RV), as well as explore novel application of left atrial 2DSTE-derived strain, rotational mechanics, and blood speckle imaging (BSI). We discuss the expanding body of literature that details methodology (feasibility and reproducibility), terminology, and reference ranges and provides a practical guide to the acquisition and interpretation of data, and explore the diagnostic/predictive ability of all these parameters with respect to neonatal cardiopulmonary health and disease.

Principles of cardiac function

In order to understand the relative strengths and weaknesses of all the measurements obtained using TDI and 2DSTE, a thorough understanding of the mechanics of cardiac performance is required. It is important to distinguish between intrinsic myocardial function (termed contractility) and pump function (termed myocardial performance). Contractility refers to the crosslinking of the actin and myosin filaments resulting in active myofiber force development and the shortening of sarcomeres. Myocardial performance or pump function describes the overall pressure development and deformation resulting in the ejection of blood from the ventricular cavity. Myocardial performance is therefore dependent on important physiological factors.

• Preload: defined as the amount of blood present in the ventricle at end-diastole before contraction begins. Up to a certain point, higher preload results in greater force generation and improved function (Frank-Starling relationship). Left and right ventricular preload are dependent primarily on pulmonary blood flow/pulmonary venous return and systemic venous return, respectively. Hydration and diastolic function are the two other important determinants.

• Afterload: also known as wall stress, is defined as the resistance against which the ventricle muscle must contract. This is primarily dependent on vascular resistance, blood viscosity, ventricular muscle wall thickness, and ventricular outflow tract obstruction. Higher afterload results in a reduction in deformation and myocardial performance, particularly in the preterm infant.

• Contractility: the intrinsic ability of the myocardial fibers to shorten as described above. This is determined by the efficiency of calcium-dependent crosslinking on the thick and thin filaments within the muscle fiber.

Tissue doppler velocity imaging

The functional measurements obtained using TDI predominantly assess myocardial performance rather than intrinsic function and as such, interpretation of values should be done in the context of the clinical situation and loading conditions. TDI filters out high-velocity signals obtained from movement of blood to focus on the lower-velocity Doppler signals of the muscle walls. TDI can be performed in pwTDI and cTDI modes ( Figure 11.1 ).

Pulsed wave tissue doppler velocity measurements

Tissue Doppler velocities can be acquired by spectral analysis using a pw Doppler technique. Muscle tissue wall moves at a much slower velocity and a higher decibel amplitude range than blood, thus facilitating a high temporal resolution, with minimal artifact from blood. Recent advances have enabled the distinction between the faster-moving blood (>50 cm/s) and slower-moving muscle tissue (<25 cm/s). pwTDI assesses longitudinal velocity of a ventricular wall segment from base to apex, providing a measure of systolic function that is recorded as the peak systolic velocity of the myocardial muscle (s′ wave). The systolic wave is usually preceded by a short upstroke during isovolumic contraction. In addition, a measure of diastolic performance can be obtained as the ventricular wall moves away from the apex in the opposite direction. The diastolic wave is biphasic and is recorded as the peak early diastolic velocity (e′ wave) and the late diastolic peak velocity (a′ wave), which reflects the active ventricular relaxation and atrial contraction phases of diastole, respectively. The diastolic waves are usually preceded by another short upstroke during isovolumic relaxation time. The duration of the isovolumic relation and contraction phases, in addition to the systolic and diastolic times, can also be accurately obtained using this modality ( Figure 11.1 ). pwTDI has high temporal resolution, but does not permit simultaneous analysis of multiple myocardial segments.

Color tissue doppler velocity

cTDI uses phase shift analysis to capture atrioventricular annular excursions. Compared with pwTDI, cTDI increases spatial resolution and provides visualization of multiple segments of the heart from one single view. It measures mean rather than peak systolic and diastolic velocities. As a result, velocities obtained using this technique are generally 20% lower in systole and diastole compared to pwTDI imaging. The two methods are therefore not interchangeable. cTDI does have the advantage of combining the high temporal resolution seen with pwTDI, with a high spatial resolution. In addition to this, myocardial velocities recorded at the left and right ventricular base, and septal wall, can be obtained from a single image for later offline analysis. A comparison between left and right ventricular function can therefore be performed. Muscle tissue at the base moves at a higher velocity than that closer to the apex. cTDI can be used to assess this velocity gradient across the wall of interest ( Figure 11.3 ). Data on cTDI values and clinical applicability in the neonatal setting are limited. This is likely due to the need for offline analysis to obtain those values and lower reproducibility when compared with pwTDI. The data presented below relate only to pwTDI.

Measurement of TDI velocities

Accurate TDI velocity measurements are highly dependent on obtaining good-quality images. This may be challenging in the neonatal setting, particularly in premature infants, where lung artifact can interfere with obtaining clear images of the walls of interest. Images are most often obtained from an apical four-chamber view but can also be acquired from the apical three- and two-chamber views. The sector width of the field of view is usually narrowed to only include the wall of interest. This ensures that the temporal resolution is enhanced and a frame rate of over 200 frames per second is obtained. A pulsed wave Doppler sample is placed at the base of the LV free wall, the base of the septum, and the base of the RV free wall. The sample gate is narrowed to only capture the velocity of the area of interest (usually 1–2 mm). It is crucial to maintain an angle of insonation of <20° to prevent underestimation of velocities. This can be most challenging for the LV free wall in infants with marked ventricular enlargement due to volume overload (e.g., hsPDA). TDI velocity measurement modality will only assess muscle movement parallel to the probe beam. This is a limitation of this modality as muscle movement perpendicular to the line of interrogation will not be assessed, and as a result, TDI velocity measurements are reserved for longitudinal (base to apex) muscle tissue movement.

As outlined above, TDI velocity assessment measures myocardial performance rather than intrinsic contractility thus, the values are highly influenced by loading conditions (in addition to intrinsic contractility). Increased preload increases systolic tissue Doppler velocities, while increased afterload reduces those velocities. Therefore clinical interpretation of those measurements must take into account the loading conditions likely to be present in the clinical situation. This has important implications for therapeutic interventions, where in some instances it may be more beneficial to improve preload (using volume support) or reduce afterload (using lusitropic medication) rather than targeting an improvement in intrinsic contractility. In addition, it is important to recognize that tissue Doppler velocity imaging cannot distinguish between active muscle movement and translational wall motion (a non-deforming segment tethered to a functioning segment). Tissue Doppler velocities may be falsely elevated, as they interrogate motion at a single point in the muscle wall with reference to the ultrasound transducer, whereas deformation imaging (see later) easily differentiates the two.