Mark R. Holland

Automated, on-line quantification of left ventricular dimensions and function by echocardiography with backscatter imaging and lateral gain compensation

To provide on-line quantification of left ventricular cavity dimensions and function by echocardiography 60 control subjects and 10 patients with cardiac dysfunction were studied. A novel, ultrasound imaging system was used which was developed to detect and track, in real time, ventricular endocardial blood boundaries based on quantitative assessment of acoustic properties of tissue. In addition, lateral gain compensation, a robust and novel image enhancement procedure, was used to provide instantaneous measurement and display of cavity areas and functional indexes on a beat-by-beat basis within regions of interest drawn around the blood pool cavity. In control subjects, short-axis end-diastolic area averaged 13.1 +/- 3.7 cm2 (SD), end-systolic area 5.9 +/- 2.7 cm2, and fractional area change 55.6 +/- 11.2%. Apical views yielded corresponding values of 23.8 +/- 4.5 cm2, 15.5 +/- 3.4 cm2 and 34.7 +/- 7.8%. Instantaneous peak rate of cavity area change approximated 50 cm2/s in systole and 60 cm2/s in diastole in each view. Serial measurements of area and functional index were reproducible over intervals of 2 to 3 weeks. Patients with dilated ventricles exhibited average apical view area values of 49.1 +/- 6.1 cm2 and 43.1 +/- 4.9 cm2 in diastole and systole with a fractional area change of 12.2 +/- 3.0%. Thus, results with on-line echocardiographic backscatter imaging-assisted automated edge detection are reproducible and capable of delineating cardiac dysfunction conveniently, promptly and serially at the bedside.

Accuracy and Reproducibility of Strain by Speckle Tracking in Pediatric Subjects with Normal Heart and Single Ventricular Physiology: A Two-Dimensional Speckle-Tracking Echocardiography and Magnetic Resonance Imaging Correlative Study

BACKGROUND Myocardial strain is a sensitive measure of ventricular systolic function. Two-dimensional speckle-tracking echocardiography (2DSE) is an angle-independent method for strain measurement but has not been validated in pediatric subjects. The aim of this study was to evaluate the accuracy and reproducibility of 2DSE-measured strain against reference tagged magnetic resonance imaging-measured strain in pediatric subjects with normal hearts and those with single ventricles (SVs) of left ventricular morphology after the Fontan procedure. METHODS Peak systolic circumferential strain and longitudinal strain (LS) in segments (n = 16) of left ventricles in age-matched and body surface area-matched 20 healthy and 12 pediatric subjects with tricuspid atresia after the Fontan procedure were measured by 2DSE and tagged magnetic resonance imaging. Average (global) and regional segmental strains measured by the two methods were compared using Spearmans and Bland-Altman analyses. RESULTS Global strains measured by 2DSE and tagged magnetic resonance imaging demonstrated close agreements, which were better for LS than circumferential strain and in normal left ventricles than in SVs (95% limits of agreement, +0.0% to +3.12%, -2.48% to +1.08%, -4.6% to +1.8%, and -3.6% to +1.8%, respectively). There was variability in agreement between regional strains, with wider limits in apical than in basal regions in normal left ventricles and heterogeneity in SVs. Strain values were significantly (P < .05) higher in normal left ventricles than in SVs except for basal LS, which were similar in both cohorts. The regional strains in normal left ventricles demonstrated an apicobasal magnitude gradient, whereas SVs showed heterogeneity. Reproducibility was the most robust for images obtained with frame rates between 60 and 90 frames/sec, global LS in both cohorts, and basal strains in normal left ventricles. CONCLUSIONS Strains measured by 2DSE agree with strain measured by magnetic resonance imaging globally but vary regionally, particularly in SVs. Global strain may be a more robust tool for cardiac functional evaluation than regional strain in SV physiology. The reliability of 2DSE-measured strain is affected by the frame rate, the nature of strain, and ventricular geometry.

Effects of myocardial fiber orientation in echocardiography: Quantitative measurements and computer simulation of the regional dependence of backscattered ultrasound in the parasternal short-axis view

We measured the regional disparity in backscattered ultrasound by means of obtaining integrated backscatter images of 10 healthy subjects and placing a region of interest in 18 distinct positions. A computer model simulating the short-axis view was implemented on the basis of previously measured values for the anisotropic ultrasonic properties of myocardium. Measurements showed that the integrated backscatter value was greatest for the anterior septum and decreased by 15.9 +/- 3.5 dB for the lateral wall and 17.7 +/- 3.5 dB for the inferior septum. The value in the posterior wall was 8.1 +/- 3.8 dB below the value for the anterior septum. The regional variation of backscatter predicted with the simulation correlated well with the clinical measurements. These results suggested that analyses based on measurements of backscatter may require compensation for the inherent anisotropic properties of myocardium.

Anomalous negative dispersion in bone can result from the interference of fast and slow waves

The goal of this work was to show that the apparent negative dispersion of ultrasonic waves propagating in bone can arise from interference between fast and slow longitudinal modes, each exhibiting positive dispersion. Simulations were carried out using two approaches: one based on the Biot-Johnson model and one independent of that model. Results of the simulations are mutually consistent and appear to account for measurements from many laboratories that report that the phase velocity of ultrasonic waves propagating in cancellous bone decreases with increasing frequency (negative dispersion) in about 90% of specimens but increases with frequency in about 10%.

Cyclic Variation of Integrated Backscatter: Dependence of Time Delay on the Echocardiographic View Used and the Myocardial Segment Analyzed

To determine the influence of myocardial anisotropy in ultrasonic tissue characterization, we measured the time delay (and magnitude) of the cyclic variation of myocardial integrated backscatter from specific segments visualized in the 4 standard transthoracic echocardiographic views. The cyclic variation data in 10 myocardial regions were obtained from analyses of 2-dimensional integrated backscatter images from 23 healthy subjects. Resultant values (mean +/- SD) for the time delay were as follows: parasternal long-axis view: 1.08 +/- 0.17 (septum) and 1.00 +/- 0.14 (posterior wall); parasternal short-axis view: 1.03 +/- 0.16 (anterior septum), 1.03 +/- 0.14 (posterior wall), 2.22 +/- 0.71 (lateral wall), and 1.65 +/- 0.66 (posterior septum); apical 4-chamber view: 1.08 +/- 0.31 (septum) and 2.20 +/- 0.79 (lateral wall); and apical 2-chamber view: 1.68 +/- 0.62 (inferior wall) and 2.04 +/- 0.72 (anterior wall). Hence, results of this study indicate that myocardial ultrasonic characterization that uses the cyclic variation is influenced by the echocardiographic view and the specific segment of the left ventricle.

Interference between wave modes may contribute to the apparent negative dispersion observed in cancellous bone

Previous work has shown that ultrasonic waves propagating through cancellous bone often exhibit a linear-with-frequency attenuation coefficient, but a decrease in phase velocity with frequency (negative dispersion) that is inconsistent with the causality-imposed Kramers-Kronig relations. In the current study, interfering wave modes similar to those observed in bone are shown to potentially contribute to the observed negative dispersion. Biot theory, the modified Biot-Attenborogh model, and experimental results are used to aid in simulating multiple-mode wave propagation through cancellous bone. Simulations entail constructing individual wave modes exhibiting a positive dispersion using plausible velocities and amplitudes, and then summing the individual modes to create mixed-mode output wave forms. Results of the simulations indicate that mixed-mode wave forms can exhibit negative dispersion when analyzed conventionally under the assumption that only one wave is present, even when the individual interfering waves exhibit positive dispersions in accordance with the Kramers-Kronig relations. Furthermore, negative dispersion is observed when little or no visual evidence of interference exists in the time-domain data. Understanding the mechanisms responsible for the observed negative dispersion could aid in determining the true material properties of cancellous bone, as opposed to the apparent properties measured using conventional data analysis techniques.

Normal Ranges of Right Ventricular Systolic and Diastolic Strain Measures in Children: A Systematic Review and Meta-Analysis

BACKGROUND Establishment of the range of normal values and associated variations of two-dimensional (2D) speckle-tracking echocardiography (STE)-derived right ventricular (RV) strain is a prerequisite for its routine clinical application in children. The objectives of this study were to perform a meta-analysis of normal ranges of RV longitudinal strain measurements derived by 2D STE in children and to identify confounders that may contribute to differences in reported measures. METHODS A systematic review was conducted in PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Search hedges were created to cover the concepts of pediatrics, STE, and the right heart ventricle. Two investigators independently identified and included studies if they reported the 2D STE-derived RV strain measure RV peak global longitudinal strain, peak global longitudinal systolic strain rate, peak global longitudinal early diastolic strain rate, peak global longitudinal late diastolic strain rate, or segmental longitudinal strain at the apical, middle, and basal ventricular levels in healthy children. Quality and reporting of the studies were assessed. The weighted mean was estimated using random effects with 95% confidence intervals (CIs), heterogeneity was assessed using Cochrans Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using funnel plots and Eggers test. Effects of demographic, clinical, equipment, and software variables were assessed in a metaregression. RESULTS The search identified 226 children from 10 studies. The reported normal mean values of peak global longitudinal strain among the studies varied from -20.80% to -34.10% (mean, -29.03%; 95% CI, -31.52% to -26.54%), peak global longitudinal systolic strain rate varied from -1.30 to -2.40 sec(-1) (mean, -1.88 sec(-1); 95% CI, -2.10 to -1.59 sec(-1)), peak global longitudinal early diastolic strain rate ranged from 1.7 to 2.69 sec(-1) (mean, 2.34 sec(-1); 95% CI, 2.00 to 2.67 sec(-1)), and peak global longitudinal late diastolic strain rate ranged from 1.00 to 1.30 sec(-1) (mean, 1.18 sec(-1); 95% CI, 1.04 to 1.33 sec(-1)). A significant base-to-apex segmental strain gradient (P < .05) was observed in the RV free wall. There was significant between-study heterogeneity and inconsistency (I(2) > 88% and P < .01 for each strain measure), which was not explained by age, gender, body surface area, heart rate, frame rate, tissue-tracking methodology, equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .59). CONCLUSIONS This study is the first to define normal values of 2D STE-derived RV strain in children on the basis of a meta-analysis. The normal mean value in children for RV global strain is -29.03% (95% CI, -31.52% to -26.54%). The normal mean value for RV global systolic strain rate is -1.88 sec(-1) (95% CI, -2.10 to -1.59 sec(-1)). RV segmental strain has a stable base-to-apex gradient that highlights the dominance of deep longitudinal layers of the right ventricle that are aligned base to apex. Variations among different normal ranges did not appear to be dependent on differences in demographic, clinical, or equipment parameters in this meta-analysis. All of the eligible studies used equipment and software from one manufacturer (GE Healthcare).

A Suggested Roadmap for Cardiovascular Ultrasound Research for the Future

Sanjiv Kaul, MD, FASE,* James G. Miller, PhD,* Paul A. Grayburn, MD, Shinichi Hashimoto,Mark Hibberd, MD, PhD, Mark R. Holland, PhD, FASE, Helene C. Houle, BA, RDMS, RDCS, RVT, FASE,Allan L. Klein, MD, FASE, Peg Knoll, RDCS, FASE, Roberto M. Lang, MD, FASE,Jonathan R. Lindner, MD, FASE, Marti L. McCulloch, RDCS, FASE, Stephen Metz, PhD,Victor Mor-Avi, PhD, FASE, Alan S. Pearlman, MD, FASE, Patricia A. Pellikka, MD, FASE, Nancy DeMarsPlambeck,BS,RDMS,RDCS,RVT,DavidPrater,MS, ThomasR.Porter,MD,FASE,DavidJ.Sahn,MD,FASE,James D. Thomas, MD, FASE, Kai E. Thomenius, PhD, and Neil J. Weissman, MD, FASEINTRODUCTIONThe leadership at the American Society of Echocardiography (ASE)decided on a proactive role in defining selected areas of researchnecessary in this decade that will meet our future clinical needs.Consequently, ASE sponsored a Technology and ResearchSummit in the fall of 2010 in conjunction with the AmericanHeart Association Scientific Sessions in Chicago. In addition to theASE executive committee, in attendance were the editor, deputyeditor, and one of the associate editors of the Journal of theAmerican Society of Echocardiography. Also invited were physician-scientists active in the field of cardiovascular ultrasound, respectedultrasound physicists, and senior engineers from the various ultra-sound companies.The agenda for the full-day meeting covered a selected range ofsubjects including the assessment of global and regional left ventricu-lar function, regional myocardialperfusion, molecular imaging, thera-peutic ultrasound, and peripheral vascular imaging. Also addressedwere research necessary to determine the broad clinical utility ofhand held ultrasound devices and the impact of future technologicaldevelopments on the field of cardiovascular imaging.Because of time constraints, other important and worthy areas ofresearch were not discussed. There was an hour devoted to the dis-cussion of each subject that was initiated by the chairs and panelistsassigned to each of the topics. The discussion was robust, and at theend, the chairs and panelists for each topic were requested to sub-mit in writing a short synopsis of the discussion. These have beencompiled into a document that we believe will serve as a roadmapfor cardiovascular ultrasound research for this decade. At the endof each section a short list of references for selected reading isprovided.Although we have defined the areas that are ripe for future re-search, we also strongly believe that we havetotrain the future scien-tists who will implement this research agenda. ASE has historicallyawarded one or two fellowship training grants a year and also anaward for researchtraining of a sonographer. At some institutions fel-lowshavealsoreceivedtraininggrantsfromthelocalAmericanHeartAssociation, and very occasionally a training grant (F32) from theNational Institutes of Health. However, this is not enough. We needmore institutional training grants from the National Institutes ofHealth in order to train an adequate number of MD and PhD scien-tists in cardiovascular imaging. To our knowledge there are currentlyonlyahandfulofsuchtraininggrantsinthecountry,whichiswoefullyinadequate. We believe that we need at least 20–25 such traininggrants devoted to the general field of cardiovascular imaging so thatwithin a decade there will be enough physicians trained in scientificmethods and clinical research to address the subjects that havebeen discussed in this report.The field of cardiovascular ultrasound is very broad, ranging fromclinical validation of new technology to studies requiring knowledgeof physics, mathematics, organic chemistry, physiology, pharmacol-ogy, molecular and vascular biology, genetics, clinical trials, and out-come research. Cross-training of individuals in one or more of thesefields is essential for cardiovascular ultrasound to thrive and succeed.Ourhopeisthatthisreportwillencourageyoungpeopletorealizethescope of cardiac ultrasound research and make a career in this dy-namic field.Selected Reading

Alterations in Ventricular Structure and Function in Obese Adolescents with Nonalcoholic Fatty Liver Disease

OBJECTIVE To determine the association among nonalcoholic fatty liver disease (NAFLD), metabolic function, and cardiac function in obese adolescents. STUDY DESIGN Intrahepatic triglyceride (IHTG) content (magnetic resonance spectroscopy), insulin sensitivity and β-cell function (5-hour oral glucose tolerance test with mathematical modeling), and left ventricular function (speckle tracking echocardiography) were determined in 3 groups of age, sex, and Tanner matched adolescents: (1) lean (n=14, body mass index [BMI]=20±2 kg/m2); (2) obese with normal (2.5%) IHTG content (n=15, BMI=35±3 kg/m2); and (3) obese with increased (8.7%) IHTG content (n=15, BMI=37±6 kg/m2). RESULTS The disposition index (β-cell function) and insulin sensitivity index were ∼45% and ∼70% lower, respectively, and whole body insulin resistance, calculated by homeostasis model of assessment-insulin resistance (HOMA-IR), was ∼60% greater, in obese than in lean subjects, and ∼30% and ∼50% lower and ∼150% greater, respectively, in obese subjects with NAFLD than those without NAFLD (P<.05 for all). Left ventricular global longitudinal systolic strain and early diastolic strain rates were significantly decreased in obese than in lean subjects, and in obese subjects with NAFLD than those without NAFLD (P<.05 for all), and were independently associated with HOMA-IR (β=0.634). IHTG content was the only significant independent determinant of insulin sensitivity index (β=-0.770), disposition index (β=-0.651), and HOMA-IR (β=0.738). CONCLUSIONS These findings demonstrate that the presence of NAFLD in otherwise asymptomatic obese adolescents is an early marker of cardiac dysfunction.

CALIBRATED QUANTITATIVE ULTRASOUND IMAGING OF SKELETAL MUSCLE USING BACKSCATTER ANALYSIS

We evaluated the ability of an ultrasound method, which can characterize cardiac muscle pathology and has reliability across different imaging systems, to obtain calibrated quantitative estimates of backscatter of skeletal muscle. Our procedure utilized a tissue‐mimicking phantom to establish a linear relationship between ultrasound grayscale and backscatter levels. We studied skeletal muscles of 82 adults: 45 controls and 37 patients with hereditary myopathies. We found that skeletal muscle ultrasound backscatter levels varied with probe orientation, age, and muscle contraction and pathology. Reliability was greater with the probe in longitudinal compared with transverse planes. Backscatter levels were higher in those >40 years of age, in muscle extension than flexion, and in myopathic patients than controls. Calibrated measurements of muscle backscatter have sensitivity and specificity in identifying and reliably measuring levels of skeletal muscle pathology. Muscle Nerve 38: 893–898, 2008