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NASA NTRS2020

Automated Cardiovascular Pathology Assessment using Semantic Segmentation and Ensemble Learning

Cardiac magnetic resonance imaging provides high spatial resolution, enabling improved extraction of important functional and morphological features for cardiovascular disease staging. Segmentation of ventricular cavities and myocardium in cardiac cine sequencing provides a basis to quantify cardiac measures such as ejection fraction. A method is presented that curtails the expense and observer bias of manual cardiac evaluation by combining semantic segmentation and disease classification into a fully automatic processing pipeline. The initial processing element consists of a robust dilated convolutional neural network architecture for voxel-wise segmentation of the myocardium and ventricular cavities. The resulting comprehensive volumetric feature matrix captures diagnostic clinical procedure data and is utilized by the final processing element to model a cardiac pathology classifier. Our approach evaluated anonymized cardiac images from a training data set of 100 patients (4 pathology groups, 1 healthy group, 20 patients per group) examined at the University Hospital of Dijon. The top average Dice index scores achieved were 0.940, 0.886, 0.849 for structure segmentation of the left ventricle (LV), myocardium and right ventricle (RV) respectively. A 5-ary pathology classification accuracy of 90% was recorded on an independent test set using the trained model. Performance results demonstrate potential for advanced machine learning methods to deliver accurate, efficient and reproducible cardiac pathological assessment.

Semantic Segmentation↗

NASA NTRS1997

Non-Invasive Measurement of Intracranial Pressure Pulsation using Ultrasound

Exposure to microgravity causes a cephalad fluid shift which may elevate intracranial pressure (ICP). Elevation in ICP may affect cerebral hemodynamics in astronauts during space flight. ICP is, however, a difficult parameter to measure due to the invasiveness of currently available techniques. We already reported our development of a non-invasive ultrasound device for measurement of ICP. We recently modified the device so that we might reproducibly estimate ICP changes in association with cardiac cycles. In the first experiment, we measured changes in cranial distance with the ultrasound device in cadavera while changing ICP by infusing saline into the lateral ventricle. In the second experiment, we measured changes in cranial distance in five healthy volunteers while placing them in 60 deg, 30 deg head-up tilt, supine, and 10 deg head-down tilt position. In the cadaver study, fast Fourier transformation revealed that cranial pulsation is clearly associated with ICP pulsation. The ratio of cranial distance and ICP pulsation is 1.3microns/mmHg. In the tilting study, the magnitudes of cranial pulsation are linearly correlated to tilt angles (r=0.87). The ultrasound device has sufficient sensitivity to detect cranial pulsation in association with cardiac cycles. By analyzing the magnitude of cranial pulsation, estimates of ICP during space flight are possible.

Ueno, Toshiaki↗

NASA NTRS2002

Numerical simulation of the influence of gravity and posture on cardiac performance

A numerical model of the cardiovascular system was used to quantify the influences on cardiac function of intrathoracic pressure and intravascular and intraventricular hydrostatic pressure, which are fundamental biomechanical stimuli for orthostatic response. The model included a detailed arterial circulation with lumped parameter models of the atria, ventricles, pulmonary circulation, and venous circulation. The venous circulation was divided into cranial, central, and caudal regions with nonlinear compliance. Changes in intrathoracic pressure and the effects of hydrostatic pressure were simulated in supine, launch, sitting, and standing postures for 0, 1, and 1.8 G. Increasing intrathoracic pressure experienced with increasing gravity caused 12% and 14% decreases in cardiac output for 1 and 1.8 G supine, respectively, compared to 0 G. Similar results were obtained for launch posture, in which the effects of changing intrathoracic pressure dominated those of hydrostatic pressure. Compared to 0 G, cardiac output decreased 0.9% for 1 G launch and 15% for 1.8 G launch. In sitting and standing, the position of the heart above the hydrostatic indifference level caused the effects of changing hydrostatic pressure to dominate those of intrathoracic pressure. Compared to 0 G, cardiac output decreased 13% for 1 G sitting and 23% for 1.8 G sitting, and decreased 17% for 1 G standing and 31% for 1.8 G standing. For a posture change from supine to standing in 1 G, cardiac output decreased, consistent with the trend necessary to explain orthostatic intolerance in some astronauts during postflight stand tests. Simulated lower body negative pressure (LBNP) in 0 G reduced cardiac output and mean aortic pressure similar to I G standing, suggesting that LBNP provides at least some cardiovascular stimuli that may be useful in preventing postflight orthostatic intolerance. A unifying concept, consistent with the Frank-Starling mechanism of the heart, was that cardiac output was proportional to cardiac diastolic transmural pressure for all postures and gravitational accelerations.

Non-NASA Center↗

NASA NTRS1997

Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance

BACKGROUND: The cardiovascular adaptation to bed rest leads to orthostatic intolerance, characterized by an excessive fall in stroke volume (SV) in the upright position. We hypothesized that this large fall in SV is due to a change in cardiac mechanics. METHODS AND RESULTS: We measured pulmonary capillary wedge pressure (PCWP), SV, left ventricular end-diastolic volume (LVEDV), and left ventricular mass (by echocardiography) at rest, during lower-body negative pressure, and after saline infusion before and after 2 weeks of bed rest with -6 degrees head-down tilt (n=12 subjects aged 24+/-5 years). Pressure (P)-volume (V) curves were modeled exponentially by P=ae(kV)+b and logarithmically by P=-Sln[(Vm-V)/(Vm-V0)], where V0 indicates volume at P=0, and the constants k and S were used as indices of normalized chamber stiffness. Dynamic stiffness (dP/dV) was calculated at baseline LVEDV. The slope of the line relating SV to PCWP during lower-body negative pressure characterized the steepness of the Starling curve. We also measured plasma volume (with Evans blue dye) and maximal orthostatic tolerance. Bed rest led to a reduction in plasma volume (17%), baseline PCWP (18%), SV (12%), LVEDV (16%), V0 (33%), and orthostatic tolerance (24%) (all P<.05). The slope of the SV/PCWP curve increased from 4.6+/-0.4 to 8.8+/-0.9 mL/mm Hg (P<.01) owing to a parallel leftward shift in the P-V curve. Normalized chamber stiffness was unchanged, but dP/dV was reduced by 50% at baseline LVEDV, and cardiac mass tended to be reduced by 5% (P<.10). CONCLUSIONS: Two weeks of head-down-tilt bed rest leads to a smaller, less distensible left ventricle but a shift to a more compliant portion of the P-V curve. This results in a steeper Starling relationship, which contributes to orthostatic intolerance by causing an excessive reduction in SV during orthostasis.

NASA Discipline Cardiopulmonary↗

NASA NTRS1973

Cardiac R-wave detector with automatic sensitivity control

An electronic circuit that automatically changes its sensitivity was developed for detecting the bioelectric signal resulting from activation of the heart's ventricles. Regulation of sensitivity was accomplished with two feedback channels that maintain the sensitivity level between an upper and a lower limit. These limits are proportional to the R-wave amplitude. Tests on an experimental circuit demonstrated a capability to reject unwanted signal noise, illustrated difficulties encountered without sensitivity control, and presented closed loop transients which occurred for step changes in R-wave amplitude.

Gebben, V. D.↗

NASA NTRS1971

Angiographic analysis of heart geometry.

Basic steps in the acquisition and reconstruction of cardiac dimensions obtained from angiocardiograms for spatial reconstruction and analysis are described, and example applications include a reconstruction of the human left ventricle and a study of the motion of the free wall of the right ventricle in a dog. Computer analysis of the spatial motion of implanted tantalum markers is discussed along with corrections for distortion and magnification incurred in the process. Graphics display of three-dimensional ventricle models is examined, and future improvements in angiocardiographic studies are considered.

Sandler, H.↗

DOE OSTI2020

Transmural Remodeling of Cardiac Microstructure in Aged Spontaneously Hypertensive Rats by Diffusion Tensor MRI

The long-standing high blood pressure (also known as hypertension) overworks the heart. Microstructural remodeling is a key factor of hypertensive heart disease progression. Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful tool for the rapid noninvasive nondestructive delineation of the cardiomyocyte organization. The spontaneously hypertensive rat (SHR) is a well-established model of genetic hypertension. The goal of this study was to employ high-resolution DT-MRI and the SHR animal model to assess the transmural layer-specific remodeling of myocardial microstructure associated with hypertension. Ex vivo experiments were performed on excised formalin-fixed hearts of aged SHRs (n = 4) and age-matched controls (n = 4). The DT-MRI-derived fractional anisotropy (FA), longitudinal diffusivity (λ L ), transversal diffusivity (λ T ), and mean diffusivity (MD) served as the readout parameters investigated at three transmural zones (i.e., endocardium, mesocardium, and epicardium). The helix angles (HAs) of the aggregated cardiomyocytes and the orientation of laminar sheetlets were also studied. Compared with controls, the SHRs exhibited decreased epicardial FA, while FA changes in the other two transmural regions were insignificant. No substantial differences were observed in the diffusivity parameters and the transmural course of HAs between the two groups. A consistent distribution pattern of laminar sheetlet orientation was not identified for either group. Our findings are in line with the known cellular microstructure from early painstaking histological studies. Biophysical explanations of the study outcomes are provided. In conclusion, our experimental findings indicate that the epicardial microstructure is more vulnerable to high blood pressure leading to more pronounced changes in this region during remodeling. DT-MRI is well-suited for elucidating these alterations. The revealed transmural nonuniformity of myocardial reorganization may shed light on the mechanisms of the microstructure-function relationship in hypertension progression. Our results provide insights into the management of patients with systemic arterial hypertension, thus prevent the progression toward heart failure. The findings of this study should be acknowledged by electromechanical models of the heart that simulate the specific cardiac pathology.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1997

Influence of simulated microgravity on the sympathetic response to exercise

Rats exposed to simulated conditions of microgravity exhibit reductions in aerobic exercise capacity that may be due to an impaired ability of the sympathetic nervous system (SNS) to mediate an increase in cardiac output and to redistribute blood flow. The purpose of this study was to quantify the sympathetic response to exercise in rats after exposure to 14 days of simulated microgravity or control conditions. To achieve this aim, rats were exposed to 14 days of head-down suspension (HDS) or cage control (CC) conditions. On day 14, norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the rate of NE depletion after synthesis blockade was used to estimate SNS activity in the left ventricle, spleen, and soleus muscle during treadmill exercise at 75% of maximal oxygen uptake. When compared with CC rats, the sympathetic response to exercise in HDS rats was characterized by a lower rate of NE depletion in the left ventricle (-82%) and spleen (-42%). The rate of NE depletion in the soleus muscle was 47% higher. These differences could contribute to the decrement in aerobic capacity of HDS rats by impairing their ability to augment cardiac output and to redirect blood flow to actively contracting skeletal muscle during exercise.

NASA Discipline Cardiopulmonary↗

DOE OSTI2021

Machine Learning Driven Contouring of High-Frequency Four-Dimensional Cardiac Ultrasound Data

Automatic boundary detection of 4D ultrasound (4DUS) cardiac data is a promising yet challenging application at the intersection of machine learning and medicine. Using recently developed murine 4DUS cardiac imaging data, we demonstrate here a set of three machine learning models that predict left ventricular wall kinematics along both the endo- and epi-cardial boundaries. Each model is fundamentally built on three key features: (1) the projection of raw US data to a lower dimensional subspace, (2) a smoothing spline basis across time, and (3) a strategic parameterization of the left ventricular boundaries. Model 1 is constructed such that boundary predictions are based on individual short-axis images, regardless of their relative position in the ventricle. Model 2 simultaneously incorporates parallel short-axis image data into their predictions. Model 3 builds on the multi-slice approach of model 2, but assists predictions with a single ground-truth position at end-diastole. To assess the performance of each model, Monte Carlo cross validation was used to assess the performance of each model on unseen data. For predicting the radial distance of the endocardium, models 1, 2, and 3 yielded average R2 values of 0.41, 0.49, and 0.71, respectively. Monte Carlo simulations of the endocardial wall showed significantly closer predictions when using model 2 versus model 1 at a rate of 48.67%, and using model 3 versus model 2 at a rate of 83.50%. These finding suggest that a machine learning approach where multi-slice data are simultaneously used as input and predictions are aided by a single user input yields the most robust performance. Subsequently, we explore the how metrics of cardiac kinematics compare between ground-truth contours and predicted boundaries. We observed negligible deviations from ground-truth when using predicted boundaries alone, except in the case of early diastolic strain rate, providing confidence for the use of such machine learning models for rapid and reliable assessments of murine cardiac function. To our knowledge, this is the first application of machine learning to murine left ventricular 4DUS data. Future work will be needed to strengthen both model performance and applicability to different cardiac disease models.

4D ultrasound↗

NASA NTRS1984

Cardiac chamber volumes by echocardiography using a new mathematical method: A promising technique for zero-G use

Accurate, reproducible, and non-invasive means for ventricular volume determination are needed for evaluating cardiovascular function zero-gravity. Current echocardiographic methods, particularly for the right ventricle, suffer from a large standard error. A new mathematical approach, recently described by Watanabe et al., was tested on 1 normal formalin-fixed human hearts suspended in a mineral oil bath. Volumes are estimated from multiple two-dimensional echocardiographic views recorded from a single point at sequential angles. The product of sectional cavity area and center of mass for each view summed over the range of angles (using a trapezoidal rule) gives volume. Multiple (8-14) short axis right ventricle and left ventricle views at 5.0 deg intervals were videotaped. The images were digitized by two independent observers (leading-edge to leading-edge technique) and analyzed using a graphics tablet and microcomputer. Actual volumes were determined by filling the chambers with water. These data were compared to the mean of the two echo measurements.

Buckey, J. C.↗

NASA NTRS1973

Regression of altitude-produced cardiac hypertrophy.

The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

Sizemore, D. A.↗

NASA NTRS2018

Automated Semantic Segmentation for Volumetric Cardiovascular Feature Quantification and Pathology Assessment

We present a pipeline method that curtails the expense and observer bias of manual cardiac evaluation by combining semantic segmentation and disease classification as a fully automatic processing pipeline. The initial element consists of a 2D U-Net convolutional neural network architecture for voxel-wise segmentation of the myocardium and ventricular cavities. The results of the segmentation were used to compute a comprehensive volumetric feature matrix that captured diagnostic clinical procedure data and that was used to model a cardiac pathology classifier.Our approach evaluated anonymized parasternal MRI cardiac images from a database of 100 patients (4 pathology groups, 1 healthy group, 20 patients per group) examined at the University Hospital of Dijon. We achieved top average Dice index scores of 0.939, 0.849, 0.886 for structure segmentation of the left ventricle (LV), right ventricle (RV) and myocardium respectively. A 5-ary pathology classification accuracy of 90% was recorded on an independent test set using our trained model.

Lindsey, Tony↗

NASA NTRS1981

Pathogenesis of sudden death following water immersion (immersion syndrome)

Sympathetic activity under cold stress is investigated. Predominantly vagal cardio-depressive reflexes are discussed besides currently known mechanisms of sudden death after water immersion. Pronounced circulatory centralization in diving animals as well as following exposure in cold water indicates additional sympathetic activity. In cold water baths of 15 C, measurements indicate an increase in plasma catecholamine levels by more than 300 percent. This may lead to cardiac arrhythmias by the following mechanisms: cold water essentially induces sinus bradycardia; brady-and tachycardiarrhythmias may supervene as secondary complications; sinusbradycardia may be enhanced by sympathetic hypertonus. Furthermore, ectopic dysrhythmias are liable to be induced by the strictly sympathetic innervation of the ventricle. Myocardial ischemia following a rise in peripheral blood pressure constitutes another arrhythmogenic factor. Some of these reactions are enhanced by alcohol intoxication.

Buhring, M.↗

NASA NTRS2010

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs

The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.

Hamilton, Douglas↗

DOE OSTI2021

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

Radiation-induced acute coronary events (ACEs) may occur as a treatment-related late adverse effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remain to be determined. The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in patients with BC treated with radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NASA NTRS2009

Acute Hemodynamic Effects of the Braslet-M Device on the International Space Station

The Braslet-M occlusion device is prescribed for cosmonauts as a countermeasure for early phases of spaceflight to temporarily alleviate symptoms associated with the cephalad fluid shift. Using a multipurpose ultrasound (US) device onboard, we assessed the acute hemodynamic effects of the Bracelet-M device on a long duration International Space Station (ISS) crewmember. Methods A combination of just-in-time training and real-time remote expert assistance was used to conduct the imaging procedures. An HDI-5000 imager (Philips, Bothell, WA) was used, provided by the ISS Human Research Facility. Superficial femoral artery (SFA), femoral vein (FV) flow spectra were obtained at mid-thigh level. Left ventricle was imaged through the apical 4-chamber view, with Color M-Mode to measure propagation velocity (V (p)). After 10 minutes of Bracelet-M use, data collection was repeated. All data were transmitted in DICOM format to ground for analysis. Results With Braslet-M, cardiac V(p) slope decreased (56ms to 42ms). A stagnation signature in the FV was seen suggesting impeded flow (rouleaux formation, too-low-to-measure velocity, and increase in diameter). Quadri-phasic flow in SFA was seen both before and after Braslet-M application. Velocities in the SFA decreased with Braslet-M (65cm/sec to 52cm/sec) and so did the time velocity integrals (16.97 to 12.4); the flow pattern spoke of resistivity increase in the vascular bed. Conclusion In the long duration ISS crewmember we observed effects of lower extremity venous occlusion through both central and peripheral indicators. A part of circulating volume transferred to peripheral potential vascular space. Impediment to venous outflow was demonstrated objectively, with a commensurate change in the flow pattern of the main feeding artery. Central volume reduction caused lower V(p). Additional studies are warranted to determine the time course of the changes and the dynamics in interstitial fluid sequestration, as well as the safe levels and duration of the compression forces.

Hamilton, Douglas R.↗

NASA NTRS2003

Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

NASA Program Biomedical Research and Countermeasur↗

NASA NTRS1987

Neurohumoral and mechanical factors in the modulation of left ventricular mass

The goals for the research were to define, describe, and study those neuroendocrine and mechanical mechanisms that may play a role in the initiation and maintenance of an increase in, or cause regression of, the mass of the left ventricle. Dynamic changes in heart mass have been observed to occur in man and animals: (1) enlargement of the heart is frequently encountered in patients with hypertensive disease, and (2) decrease in heart mass has been reported for men exposed to prolonged space flight. The basic physiologic processes which may explain how these changes occur, and the effects of gain or loss of myocardial mass on cardiac performance were considered significant questions to be answered for the benefit of the National Aeronautics and Space Administration.

Franklin, Eleanor I.↗