Notice of Removal: 3D myocardial mechanical wave measurements using high frame rate ultrasound imaging and Clutter filter wave imaging: Towards a 3D myocardial elasticity mapping

Introduction Premenopausal women with intermediate-high risk HR+ breast cancer often receive near-complete estrogen deprivation with ovarian function suppression concurrent with an AI. Hypoestrogenemia is associated with cardiotoxicity, but the cardiovascular impact of this newer breast cancer treatment is largely unknown. With increases in survival rates and younger women being diagnosed, methods to monitor and predict cardiac damage due to OFS+AI therapy are needed. Left ventricle (LV) ejection fraction is currently used for monitoring cancer treatment-related cardiovascular degradation, and can detect major heart defects, but is insensitive to subclinical left ventricle function. Emerging methods include T1 mapping and estimation of myocardial strain to indicate fibrosis. We propose an extension of these methods by estimating cardiac tissue elasticity using LV wall deformation to drive a biomechanical model. Elasticity is a more functional and direct measurement of tissue response based on structural mechanics driven by patient-specific cardiac magnetic resonance imaging (CMR) data. Elasticity measurements may serve as a predictive biomarker of early AI-induced cardiac changes.MethodsThis study is a retrospective initial proof-of-concept correlative imaging study to an existing clinical study for the use of CMR to detect cardiovascular damage (ESPRIT). Two cohorts of premenopausal breast cancer patients either: (1) undergoing OFS+AI for HR+ breast cancer or (2) triple negative breast cancer (TNBC) patients that have already received chemotherapy, were imaged twice, 3-6 months apart using CINE CMR. TNBC patients serve as the control, with no expectation of further cancer treatment-related cardiac damage. Time steps during passive ventricular diastole were visually selected from CINE CMRs. Each slice was non-rigidly registered to estimate LV deformation during passive filling. Deformation was simulated on a finite element mesh of the LV based on linear elastic transverse isotropic mechanical equilibrium. Using an inverse problem formulation, simulated deformation was compared to model-calculated deformation to estimate the spatial tissue longitudinal and transverse elasticity. Elasticity maps of the LV at initial and final points are compared to determine regional stiffening of the LV wall, to be used as early biomarkers for LV fibrosis. ResultsIn this initial investigation, elasticity maps were analyzed for four patients (n=2 from each cohort). Passive LV tissue stiffening was observed in each AI patient, with 100% and 25% relative increases observed for longitudinal elasticity and 50% increases for transverse elasticity in the basal inferior region, and mid anterior region of the LV in each patient, respectively. No increases in stiffness of the LV were observed for TNBC patients. Ejection fraction remained consistent for all patients. ConclusionIn this proof-of-concept study, we demonstrate that elasticity maps indicate local stiffening of the LV using a biomechanical model-based elasticity imaging method that could be used to indicate cardiac dysfunction in breast cancer patients receiving AIs. Spatial elasticity mapping allows direct observation of structural mechanics to reveal specific areas of LV stiffening. Moving beyond traditional strain imaging, our method yields a functional measure of tissue stiffness to directly indicate cardiac fibrosis. This study demonstrates the use of biomechanical models to interpret CMR and provides potential for use of more advanced constitutive models. Our non-invasive biomechanical model-based elasticity imaging method shows significant promise to indicate early cardiac function deterioration, critical for premenopausal women undergoing extended cancer therapies. Citation Format: Caroline Elizabeth Miller, Jennifer Jordan, Alexandra Thomas, Jared Weis. Predicting cardiac dysfunction in breast cancer patients undergoing aromatase inhibitor treatment using biomechanical model-based elasticity imaging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS3-21.

The elastic properties of human tissue can be evaluated through the study of mechanical wave propagation captured using high frame rate ultrasound imaging. Methods such as block-matching or phase-based motion estimation have been used to estimate the displacement induced by the mechanical waves. In this paper, a new method for detecting mechanical wave propagation without motion estimation is presented, where the motion of interest is accentuated by an appropriate clutter filter. Thus, the mechanical wave propagation will directly appear as bands of the attenuated signal moving in the B-mode sequence and corresponding anatomical M-mode images. While only the locality of tissue velocity induced by the mechanical wave is detected, it is shown that the method is more sensitive to subtle tissue displacements when compared to motion estimation techniques. The technique was evaluated for the propagation of the pulse wave in a carotid artery, mechanical waves on the left ventricle, and shear waves induced by radiation force on a tissue-mimicking phantom. The results were compared to tissue Doppler imaging (TDI) and demonstrated that clutter filter wave imaging (CFWI) was able to detect the mechanical wave propagating in tissue with a relative temporal and spatial resolution 30% higher and a relative consistency 40% higher than TDI. The results showed that CFWI was able to detect mechanical waves with a relative frequency content 40% higher than TDI in a shear wave imaging experiment.

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is today hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to the 2-D mapping of temperature changes during HIFU treatments. This new concept of shear wave thermometry is experimentally implemented here using conventional ultrasonic imaging probes. HIFU treatment and monitoring were, respectively, performed using a confocal setup consisting of a 2.5-MHz single-element transducer focused at 30 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Thermocouple measurements and ultrasound-based thermometry were used as a gold standard technique and were combined with SWI on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created using 100-μs pushing beams at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Elasticity and temperature mapping was achieved every 3 s, leading to realtime monitoring of the treatment. Tissue stiffness was found to decrease in the focal zone for temperatures up to 43°C. Ultrasound-based temperature estimation was highly correlated to stiffness variation maps (r² = 0.91 to 0.97). A reversible calibration phase of the changes of elasticity with temperature can be made locally using sighting shots. This calibration process allows for the derivation of temperature maps from shear wave imaging. Compared with conventional ultrasound-based approaches, shear wave thermometry is found to be much more robust to motion artifacts.

For normal cardiac performance, the left ventricle (LV) must be able to eject an adequate stroke volume at arterial pressure (systolic function) and fill without requiring an elevated left atrial (LA) pressure (diastolic function). These systolic and diastolic functions must be adequate to meet the needs of the body both at rest and during stress. Response by Tschope and Paulus on p 809 Systolic function is conveniently (although not always accurately) measured as the ejection fraction (EF), calculated as stroke volume divided by end-diastolic volume.1 The LV EF is easily interpreted. The lower limit of normal is ≈50%. The lower the EF is, the greater the reduction in systolic function. Diastolic function has been more difficult to evaluate.2 Traditionally, invasive measures of LV diastolic pressure-volume relations and the rate of LV pressure fall during isovolumetric relaxation have been used. However, these methods are not practical for routine clinical use and do not adequately evaluate all aspects of diastolic filling.3 Comprehensive echocardiographic evaluation of the dynamics of LV filling using blood pool and tissue Doppler has now progressed so that it provides clinically important information that can be used to direct patient care. We present data that support the use of echocardiographic evaluation of diastolic function to recognize cardiac dysfunction in patients with heart failure, especially those with preserved EF; to guide the management of patients by identifying those with and without elevated left filling pressures regardless of underlying EF; and to determine prognosis in a wide variety of patient populations. Although the LV end-diastolic pressure-volume relation describes the passive properties of the LV, LV filling is not a passive or slow process.3 In fact, the peak flow rate across the mitral valve is equal to or greater than the peak flow rate across the aortic valve. …

Background Heart failure (HF) causes liver congestion, which is thought to increase liver stiffness. Elastography is a noninvasive method of measuring organ stiffness that was originally developed to evaluate fibrosis caused by liver diseases such as cirrhosis. There are two main techniques of elastography: shear wave imaging and strain imaging. Shear wave imaging varies significantly due to the influence of not only fibrosis but also congestion, inflammation, and jaundice. In contrast, strain imaging in chronic liver disease reflects only the progression of liver fibrosis. We previously presented a method that is measuring both shear wave and strain imaging (combinational elastography) for assessing liver congestion. This study demonstrates the prognostic impact and severity assessment of combinational elastography in HF patients. Methods This study included 144 HF patients (age 76.4±12.3, men 67). The velocity of shear wave (Vs) values was measured with shear wave imaging. Fibrosis index (F Index) was calculated by measuring both shear wave and strain imaging. Results During a median follow-up of 161 days, 14 deaths or hospitalization for HF was observed. A multivariable cox regression analysis demonstrated that high vs values was dependently correlated with higher mortality rate and HF hospitalization (hazard ratio: 2.31; 95% confidence interval: 1.09–4.89; p=0.029). The Kaplan-Meier analysis demonstrated that high vs (>1.87 m/s) was associated with higher hospitalization rates for HF compared with low vs (≤1.87 m/s, log rank test, p<0.001). F index showed graded elevation as stage of HF progressed (stage A or B, C, D: 1.19±0.43, 1.38±0.56, 2.8±1.32; p<0.001). Conclusion Combinational elastography can predict the severity of HF.

Percutaneous Transcatheter Closure of the Aortic Valve to Treat Cardiogenic Shock in a Left Ventricular Assist Device Patient With Severe Aortic Insufficiency

Shear Wave Imaging (SWI) is an ultrasound based technique for elasticity imaging that has been successfully tested on several organs in the framework of cancer diagnosis. In this work, the potential of this technique to map brain elasticity in vivo on trepanned small animals is investigated. From a SWI scan of the rat brain, 3D elasticity maps are reconstructed reaching a spatial resolution of 800 μm. The dynamic modulus of the brain tissues exhibits values in the 1 to 16 kPa range and is quantified for different anatomical regions. The propagation of shear waves is found to be anisotropic, which could be a consequence of fiber orientation. Finally, the interest of brain elasticity mapping for the monitoring of brain ischemia is investigated on a rat model. Focal cerebral ischemia is shown to induce a dramatic decrease of elasticity in the lesion.

Electromechanical dyssynchrony can markedly worsen heart failure (HF) morbidity and mortality, independent of traditional risk factors.1–4 Depending on the metric used, current estimates of the prevalence of dyssynchrony vary from 25–30% in patients with HF (based on QRS widening) up to 60%, based on tissue Doppler or MRI measures of dyssynchronous contraction of the left ventricle (LV).5,6 Cardiac resynchronization therapy (CRT) or biventricular pacing has emerged as a promising option to treat patients with HF and dyssynchronous contraction.7–9 The past few decades have seen the rise of pharmacotherapy, primarily through agents that antagonize the effect of excessive concentrations of circulating neurohormones, yet, HF-related morbidity and mortality remain high.3–6 Biventricular stimulation has been demonstrated to improve contractile performance in patients with mechanical dyssynchrony acutely and chronically while also prolonging long-term survival—something not yet achieved by drug therapy.10 Although the clinical and mechanical effectiveness of CRT are well described, 30% of patients do not benefit from CRT and clinical criteria to identify CRT nonresponders remain elusive8,11,12 Currently, the most widely used predictor of reverse remodeling is the presence of marked mechanical dyssynchrony before CRT, as indexed by the width of the QRS.13 Mechanical dyssynchrony seems important, yet imaging-based measures have not predicted response well14 and even improvement in dyssynchrony after initiation of CRT only weakly predicts chronic response.15 Limited understanding of the molecular mechanisms underlying reverse cardiac remodeling induced by CRT has hampered the selection of potential responders. In this review, we focus on the electrophysiological aspects and molecular networks underlying the benefits of CRT. We will review how CRT homogenizes regional differences in stress kinase signaling and electric remodeling and then review its global effect on myocyte function and its …

Comments on Point:Counterpoint: Left ventricular volume during diastasis is/is not the physiological in vivo equilibrium volume and is/is not related to diastolic suction

Background/introduction Mechanical waves within the myocardium arising from physiologic events in the cardiac cycle such as the atrial kick (AK), mitral valve closure (MVC) and aortic valve closure (AVC) offer insight to tissue stiffness and can be measured by high frame rate echocardiography. Purpose To investigate the feasibility of measuring mechanical wave velocities in the left ventricle by clutter filter wave imaging (CFWI) and its potential for detecting regional myocardial dysfunction in patients with acute coronary syndrome. Methods We examined 60 patients (66±9 years of age, 72% male) with acute coronary syndrome by high frame rate echocardiography after revascularisation, imaging the left ventricle from the parasternal long axis view and three apical projections. Intrinsic mechanical waves generated by the AK, MVC and AVC were analysed off-line by CFWI of all walls using custom software (PyMWI) on 2000 frames of in-phase and quadrature component data per view extracted from a Vivid E95 scanner. Results We analysed a total number of 2372 waves recorded with a frame rate of 1180 (1134-1199) frames per second. The feasibility for measuring AK waves was high in all regions (mean 89%), but lower for the MVC and AVC waves with significant variability between regions (mean 44% and 46%, respectively; p<0.001). Feasibility declined from basal to apical segments for all waves (p=0.0001). Mean mechanical wave velocity was slowest for the AK wave at 2.5 (2.0-3.0) m/s, faster for the AVC wave at 5.1 (3.5-6.3) m/s and fastest for the MVC wave at 6.6 (4.9-8.6) m/s (p=0.0001). Basal AK wave velocity was faster in patients with basal wall motion abnormalities compared to those without (2.7 vs. 2.0 m/s, p=0.0004) and could detect the presence of wall motion abnormalities adjusting for age, gender and parameters of diastolic function (univariable OR 3.4, 95% CI 1.5-7.7, p<0.01; multivariable OR 4.4, 95% CI 1.4-14.1, p=0.01). Basal AK wave velocity detected wall motion abnormalities with an AUC of 0.78 with cut-off speeds of 2.3 m/s and 3.0 m/s, both correctly classifying 73% of cases (sensitivity/specificity 81%/68% and 43%/89%, respectively). Mechanical wave velocities of other waves and in other regions were not consistently and only weakly associated with echocardiographic parameters of systolic and diastolic function. Conclusion(s) Mechanical wave velocities by CFWI detects myocardial dysfunction in acute coronary syndrome. Elevated basal AK wave velocity was independently associated with myocardial dysfunction where AK wave velocity ≥2.3 m/s provided a good sensitivity and ≥3.0 m/s a good specificity for detecting regional wall motion abnormalities. The feasibility of measuring the AK wave was good, whereas MVC and AVC waves had lower feasibility and were inadequate for assessment of myocardial function. Feasibility variations between AK and MVC/AVC waves suggest differences in wave propagation dynamics or intrinsic wave properties.Illustration Clutter Filter Wave ImagingRisk of myocardial dysfunction

Mechanical Wave Velocities in Left Ventricular Walls in Healthy Subjects and Patients With Aortic Stenosis

Shear wave elastography is a distinctive method to access the viscoelastic characteristic of the soft tissue that is difficult to obtain by other imaging modalities. This paper proposes a novel shear wave elastography [color Doppler shear wave imaging (CD SWI)] for breast tissue. Continuous shear wave is produced by a small lightweight actuator, which is attached to the tissue surface. Shear wave wavefront that propagates in tissue is reconstructed as a binary pattern that consists of zero and the maximum flow velocities on color flow image (CFI). Neither any modifications of the ultrasound color flow imaging instrument nor a high frame rate ultrasound imaging instrument is required to obtain the shear wave wavefront map. However, two conditions of shear wave displacement amplitude and shear wave frequency are needed to obtain the map. However, these conditions are not severe restrictions in breast imaging. This is because the minimum displacement amplitude is [Formula: see text] for an ultrasonic wave frequency of 12 MHz and the shear wave frequency is available from several frequencies suited for breast imaging. Fourier analysis along time axis suppresses clutter noise in CFI. A directional filter extracts shear wave, which propagates in the forward direction. Several maps, such as shear wave phase, velocity, and propagation maps, are reconstructed by CD SWI. The accuracy of shear wave velocity measurement is evaluated for homogeneous agar gel phantom by comparing with the acoustic radiation force impulse method. The experimental results for breast tissue are shown for a shear wave frequency of 296.6 Hz.

Quantitative Viscoelasticity Mapping of Human Liver Using Supersonic Shear Imaging: Preliminary In Vivo Feasability Study

Why is heart failure in children important? If we just consider the number of individuals affected, adult heart failure is clearly a more compelling public health problem. However, the relatively small numbers belie the overall economic and social impact of pediatric heart failure. When a child is admitted to the hospital for heart failure, the costs are considerably higher for children than adults because of the frequent need for surgical or catheter-based intervention. The demands of medical care can fray the family structure and adversely affect parental economic productivity. When a child dies of heart failure, the economic impact is magnified enormously because of the number of potentially productive years lost per death. For these and other reasons, heart failure in children is a serious public health concern. In addition, growing numbers of children with heart failure are reaching adulthood because of the successful application of medical and surgical heart failure therapies and the improved outcomes of congenital heart surgery. A greater understanding of the pathophysiology of heart failure in childhood may help inform therapeutic strategies once these children become adults. Furthermore, given the recent explosion of research in the impact of cardiac development and cardiogenetics on pediatric cardiovascular disease, it is not outside the realm of possibility for a pediatric discovery to be made that will also benefit adults with heart failure. We may not yet be able to agree on a definition of heart failure, but the cardinal symptoms, dyspnea, anasarca (“dropsy”), and cachexia, were well recognized in antiquity.1 These symptoms were not specific for cardiac pathology, and it was not until the 17th century, when William Harvey definitively identified the heart as an organ that pumped blood rather than generating heat, that the heart could begin to be understood as a source of dyspnea, edema, and …

Over the last 2 decades, numerous advancements in medical therapies have improved patient outcomes in heart failure (HF). However, a significant number of patients still progress to end-stage HF, in which treatment options are largely limited to cardiac transplantation. As patient demands for transplant continue to exceed the supply of available organs, mechanical assist devices—specifically, the left ventricular assist device (LVAD)—were initially introduced as a bridge to cardiac transplantation. LVADs have 2 important beneficial effects. First, LVADs are placed in parallel to the native left ventricle (LV), causing pressure and volume unloading of the LV. Second, LVADs restore cardiac output and subsequent perfusion to the organs. As a result of these 2 effects, it became evident that some patients had actual improvement in LV function after LVAD placement. The term reverse remodeling was used to describe the improvement in myocardial function that was observed in patients with a seemingly end-stage disease. With reverse remodeling, a new hope for the treatment of HF was born—using LVADs as a bridge to recovery; however, to date, this promise has largely been unrealized. This probably is reflective of the fact that the sequela of mechanical ventricular unloading are quite complex and appear to involve the engagement of competing biological pathways including regression of cardiomyocyte hypertrophy as well as progressive cell atrophy. Although the promise of ventricular recovery still persists, its actualization will await a more comprehensive dissection of these competing biological processes. This review will discuss the beneficial clinical effects of LVAD support as well as review what is known about the cellular and molecular response to mechanical unloading and mechanisms of reverse remodeling. Key research findings have been summarized in the Table. View this table: Table. Summary of Research of LVAD Support on Clinical Effects and the Cellular and Molecular Changes That May Contribute to Reverse …