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Autism Spectrum Disorder (ASD) is characterized as a neurodevelopmental disorder with a heterogeneous nature, influenced by genetics and exhibiting diverse clinical presentations. In this study, we dissect Autism Spectrum Disorder (ASD) into its behavioral components, mirroring the diagnostic process used in clinical settings. Morphological features are extracted from magnetic resonance imaging (MRI) scans, found in the publicly available dataset ABIDE II, identifying the most discriminative features that differentiate ASD within various behavioral domains. Then, each subject is categorized as having severe, moderate, or mild ASD, or typical neurodevelopment (TD), based on the behavioral domains of the Social Responsiveness Scale (SRS). Through this study, multiple artificial intelligence (AI) models are utilized for feature selection and classifying each ASD severity and behavioural group. A multivariate feature selection algorithm, investigating four different classifiers with linear and non-linear hypotheses, is applied iteratively while shuffling the training-validation subjects to find the set of cortical regions with statistically significant association with ASD. A set of six classifiers are optimized and trained on the selected set of features using 5-fold cross-validation for the purpose of severity classification for each behavioural group. Our AI-based model achieved an average accuracy of 96%, computed as the mean accuracy across the top-performing AI models for feature selection and severity classification across the different behavioral groups. The proposed AI model has the ability to accurately differentiate between the functionalities of specific brain regions, such as the left and right caudal middle frontal regions. We propose an AI-based model that dissects ASD into behavioral components. For each behavioral component, the AI-based model is capable of identifying the brain regions which are associated with ASD as well as utilizing those regions for diagnosis. The proposed system can increase the speed and accuracy of the diagnostic process and result in improved outcomes for individuals with ASD, highlighting the potential of AI in this area., (© 2023. Springer Nature Limited.)

Patients with single ventricle defects undergoing the Fontan procedure eventually face Fontan failure. Long-term cavopulmonary assist devices using rotary pump technologies are currently being developed as a subpulmonary power source to prevent and treat Fontan failure. Low hydraulic resistance is a critical safety requirement in the event of pump failure (0 RPM) as a modest 2 mmHg cavopulmonary pressure drop can compromise patient hemodynamics. The goal of this study is therefore to assess the passive performance of a viscous impeller pump (VIP) we are developing for Fontan patients, and validate flow simulations against in-vitro data. Two different blade heights (1.09 mm vs 1.62 mm) and a blank housing model were tested using a mock circulatory loop (MCL) with cardiac output ranging from 3 to 11 L/min. Three-dimensional flow simulations were performed and compared against MCL data. In-silico and MCL results demonstrated a pressure drop of < 2 mmHg at a cardiac output of 7 L/min for both blade heights. There was good agreement between simulation and MCL results for pressure loss (mean difference - 0.23 mmHg 95% CI [0.24-0.71]). Compared to the blank housing model, low wall shear stress area and oscillatory shear index on the pump surface were low, and mean washout times were within 2 s. This study demonstrated the low resistance characteristic of current VIP designs in the failed condition that results in clinically acceptable minimal pressure loss without increased washout time as compared to a blank housing model under normal cardiac output in Fontan patients., (© 2023. Springer Nature Limited.)

Continuous flow rotary blood pumps (RBP) operating clinically at constant rotational speeds cannot match cardiac demand during varying physical activities, are susceptible to suction, diminish vascular pulsatility, and have an increased risk of adverse events. A sensorless, physiologic feedback control strategy for RBP was developed to mitigate these limitations. The proposed algorithm used intrinsic pump speed to obtain differential pump speed (Δ RPM ). The proposed gain-scheduled proportional-integral controller, switching of setpoints between a higher pump speed differential setpoint (Δ RPM Hr ) and a lower pump speed differential setpoint (Δ RPM Lr ), generated pulsatility and physiologic perfusion, while avoiding suction. The switching between Δ RPM Hr and Δ RPM Lr setpoints occurred when the measured Δ RPM reached the pump differential reference setpoint. In-silico tests were implemented to assess the proposed algorithm during rest, exercise, a rapid 3-fold pulmonary vascular resistance increase, rapid change from exercise to rest, and compared with maintaining a constant pump speed setpoint. The proposed control algorithm augmented aortic pressure pulsatility to over 35 mmHg during rest and around 30 mmHg during exercise. Significantly, ventricular suction was avoided, and adequate cardiac output was maintained under all simulated conditions. The performance of the sensorless algorithm using estimation was similar to the performance of sensor-based method. This study demonstrated that augmentation of vascular pulsatility was feasible while avoiding ventricular suction and providing physiological pump outflows. Augmentation of vascular pulsatility can minimize adverse events that have been associated with diminished pulsatility. Mock circulation and animal studies would be conducted to validate these results., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Bladder cancer (BC) is the 10th most common cancer globally and has a high mortality rate if not detected early and treated promptly. Non-muscle-invasive BC (NMIBC) is a subclassification of BC associated with high rates of recurrence and progression. Current tools for predicting recurrence and progression on NMIBC use scoring systems based on clinical and histopathological markers. These exclude other potentially useful biomarkers which could provide a more accurate personalized risk assessment. Future trends are likely to use artificial intelligence (AI) to enhance the prediction of recurrence in patients with NMIBC and decrease the use of standard clinical protocols such as cystoscopy and cytology. Here, we provide a comprehensive survey of the most recent studies from the last decade (N = 70 studies), focused on the prediction of patient outcomes in NMIBC, particularly recurrence, using biomarkers such as radiomics, histopathology, clinical, and genomics. The value of individual and combined biomarkers is discussed in detail with the goal of identifying future trends that will lead to the personalized management of NMIBC.

There is need for a reliable in vitro system that can accurately replicate the cardiac physiological environment for drug testing. The limited availability of human heart tissue culture systems has led to inaccurate interpretations of cardiac-related drug effects. Here, we developed a cardiac tissue culture model (CTCM) that can electro-mechanically stimulate heart slices with physiological stretches in systole and diastole during the cardiac cycle. After 12 days in culture, this approach partially improved the viability of heart slices but did not completely maintain their structural integrity. Therefore, following small molecule screening, we found that the incorporation of 100 nM tri-iodothyronine (T3) and 1 μM dexamethasone (Dex) into our culture media preserved the microscopic structure of the slices for 12 days. When combined with T3/Dex treatment, the CTCM system maintained the transcriptional profile, viability, metabolic activity, and structural integrity for 12 days at the same levels as the fresh heart tissue. Furthermore, overstretching the cardiac tissue induced cardiac hypertrophic signaling in culture, which provides a proof of concept for the ability of the CTCM to emulate cardiac stretch-induced hypertrophic conditions. In conclusion, CTCM can emulate cardiac physiology and pathophysiology in culture for an extended time, thereby enabling reliable drug screening., (© 2022. The Author(s).)

Rotary left ventricular assist devices (LVAD) have emerged as a long-term treatment option for patients with advanced heart failure. LVADs need to maintain sufficient physiological perfusion while avoiding left ventricular myocardial damage due to suction at the LVAD inlet. To achieve these objectives, a control algorithm that utilizes a calculated suction index from measured pump flow (SIMPF) is proposed. This algorithm maintained a reference, user-defined SIMPF value, and was evaluated using an in silico model of the human circulatory system coupled to an axial or mixed flow LVAD with 5-10% uniformly distributed measurement noise added to flow sensors. Efficacy of the SIMPF algorithm was compared to a constant pump speed control strategy currently used clinically, and control algorithms proposed in the literature including differential pump speed control, left ventricular end-diastolic pressure control, mean aortic pressure control, and differential pressure control during (1) rest and exercise states; (2) rapid, eight-fold augmentation of pulmonary vascular resistance for (1); and (3) rapid change in physiologic states between rest and exercise. Maintaining SIMPF simultaneously provided sufficient physiological perfusion and avoided ventricular suction. Performance of the SIMPF algorithm was superior to the compared control strategies for both types of LVAD, demonstrating pump independence of the SIMPF algorithm.

Patients with heart failure (HF) or undergoing cardiogenic shock and percutaneous coronary intervention require short-term cardiac support. Short-term cardiac support using a left ventricular assist device (LVAD) alters the pressure and flows of the vasculature by enhancing perfusion and improving the hemodynamic performance for the HF patients. However, due to the position of the inflow and outflow of the LVAD, the local hemodynamics within the aorta is altered with the LVAD support. Specifically, blood velocity, wall shear stress, and pressure difference are altered within the aorta. In this study, computational fluid dynamics (CFD) was used to elucidate the effects of a short-term LVAD for hemodynamic performance in a patient-specific aorta model. The three-dimensional (3D) geometric models of a patient-specific aorta and a short-term LVAD, Impella CP, were created. Velocity, wall shear stress, and pressure difference in the patient-specific aorta model with the Impella CP assistance were calculated and compared with the baseline values of the aorta without Impella CP support. Impella CP support augmented cardiac output, blood velocity, wall shear stress, and pressure difference in the aorta. The proposed CFD study could analyze the quantitative changes in the important hemodynamic parameters while considering the effects of Impella CP, and provide a scientific basis for further predicting and assessing the effects of these hemodynamic signals on the aorta., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Wang, Peng, Huo, Yang, Giridharan, Luan and Qin.)

Liver cancer is a major cause of morbidity and mortality in the world. The primary goals of this manuscript are the identification of novel imaging markers (morphological, functional, and anatomical/textural), and development of a computer-aided diagnostic (CAD) system to accurately detect and grade liver tumors non-invasively. A total of 95 patients with liver tumors (M = 65, F = 30, age range = 34-82 years) were enrolled in the study after consents were obtained. 38 patients had benign tumors (LR1 = 19 and LR2 = 19), 19 patients had intermediate tumors (LR3), and 38 patients had hepatocellular carcinoma (HCC) malignant tumors (LR4 = 19 and LR5 = 19). A multi-phase contrast-enhanced magnetic resonance imaging (CE-MRI) was collected to extract the imaging markers. A comprehensive CAD system was developed, which includes the following main steps: i) estimation of morphological markers using a new parametric spherical harmonic model, ii) estimation of textural markers using a novel rotation invariant gray-level co-occurrence matrix (GLCM) and gray-level run-length matrix (GLRLM) models, and iii) calculation of the functional markers by estimating the wash-in/wash-out slopes, which enable quantification of the enhancement characteristics across different CE-MR phases. These markers were subsequently processed using a two-stages random forest-based classifier to classify the liver tumor as benign, intermediate, or malignant and determine the corresponding grade (LR1, LR2, LR3, LR4, or LR5). The overall CAD system using all the identified imaging markers achieved a sensitivity of 91.8%±0.9%, specificity of 91.2%±1.9%, and F[Formula: see text] score of 0.91±0.01, using the leave-one-subject-out (LOSO) cross-validation approach. Importantly, the CAD system achieved overall accuracies of [Formula: see text], 85%±2%, 78%±3%, 83%±4%, and 79%±3% in grading liver tumors into LR1, LR2, LR3, LR4, and LR5, respectively. In addition to LOSO, the developed CAD system was tested using randomly stratified 10-fold and 5-fold cross-validation approaches. Alternative classification algorithms, including support vector machine, naive Bayes classifier, k-nearest neighbors, and linear discriminant analysis all produced inferior results compared to the proposed two stage random forest classification model. These experiments demonstrate the feasibility of the proposed CAD system as a novel tool to objectively assess liver tumors based on the new comprehensive imaging markers. The identified imaging markers and CAD system can be used as a non-invasive diagnostic tool for early and accurate detection and grading of liver cancer.

In the US, the most significant morbidity and mortality associated with non-valvular atrial fibrillation (NVAF) is embolic stroke, with 90% of thrombus originating from the left atrial appendage (LAA). Anticoagulation is the preferred treatment for the prevention of stroke in NVAF patients, but clinical studies have demonstrated high levels of non-compliance and increased risk of bleeding or ineligibility for anticoagulation therapy, especially in the elderly population where the incidence of NVAF is highest. Alternatively, stroke may be preventing using clinically approved surgical and catheter-based devices to exclude or occlude the LAA, but these devices continue to be plagued by peri-device leaks and thrombus formation because of residual volume. To overcome these limitations, Cor Habere (Louisville, KY) and the University of Louisville are developing a LAA closure device (StrokeShield) that completely occludes and collapses the LAA to minimize the risk of stroke. The StrokeShield device is a collapsible occluder (nitinol reinforced membrane) that completely covers the LAA orifice with an expandable conical coil anchor that attaches to the myocardium. The device is designed for catheter-based delivery and expands to completely occlude the LAA orifice and collapse the LAA. The primary advantages of the StrokeShield system are a completely sealed LAA (no peri-device flow or residual space) and smooth endothelialized connection to the left atrial wall with minimal risk of cardiac bleeding and tamponade. We tested proof-of-concept of a prototype StrokeShield device in acute (n = 2) and chronic 60-day (n = 2) healthy canine models. Acute results demonstrated that the conical coil securely attached to the myocardium (5N pull-out force) and the Nitinol umbrella fully deployed and covered the LAA ostium. Results from the chronic implants demonstrated long-term feasibility of device placement with no procedural or device-related intra- or post-operative complications, secure placement and correct positioning of the device with no device migration. The device successfully occluded the LAA ostium and collapsed the LAA with no interference with the mitral valve, circumflex coronary artery, or pulmonary veins. Necropsy demonstrated no gross signs of thrombus or end-organ damage and the device was encapsulated in the LAA. Histology demonstrated mature neointima covering the device with expected foreign body inflammatory response. These early positive results will help to guide the iterative design process for the continued development of the StrokeShield system., Competing Interests: Financial • Two US patents awarded related to the research presented in this manuscript, and a third University of Louisville (UofL) invention disclosure was filed February 1, 2021, but is not presented in this manuscript Slaughter MS, Giridharan GA, Sobieski MA, Soucy KG, and Koenig SC. Atrial appendage closure device and related methods (US Patent 10,531,878 awarded January 14, 2020) Slaughter MS, Giridharan GA, Sobieski MA, Soucy KG, and Koenig SC. Atrial appendage closure device and related methods (US Patent 10,898,202 awarded January 26, 2021) Slaughter MS, Monreal G, Koenig SC, Jimenez J, Tompkins L. Left Atrial Appendage (LAA) device, delivery tool, and related methods (UofL Invention Disclosure no. 21038, filed February 1, 2021) • Research presented in this manuscript was funded as an internal project subaward (PI: Guruprasad Giridharan) from a 5-yr Coulter Foundation grant awarded to University of Louisville (PIs: Robert Keynton, PhD and Mark Slaughter, MD) • Co-authors Jimenez, Koenig, Slaughter are co-founders of Cor Habere (Louisville KY), and are continuing the research and development of the StrokeShield system (LAA device) presented in this manuscript. Note: Cor Habere was founded after the research and development presented in this manuscript had been completed. • Cor Habere was awarded a NIH SBIR phase I grant (R43HL142337-01) to continue development of the StrokeShield system (LAA device, delivery tool) but none of the work supported by the SBIR phase I grant is presented in this manuscript. Co-authors (Giridharan, Koenig, Slaughter) were awarded US Patent 10,531,878 (January 14, 2020) and US Patent 10,898,202 (January 26, 2021). All of the co-authors are continuing with the development of the StrokeShield device and are listed as co-inventors on our recent UofL invention disclosure (no. 21038, filed Feb 1, 2021) and co-investigators of NIH SBIR phase I grant (R43HL142337-01, awarded Sep 30, 2019). This information does NOT alter our adherence to PLOS ONE policies on sharing data and materials.

The primary goal of this manuscript is to develop a computer assisted diagnostic (CAD) system to assess pulmonary function and risk of mortality in patients with coronavirus disease 2019 (COVID-19). The CAD system processes chest X-ray data and provides accurate, objective imaging markers to assist in the determination of patients with a higher risk of death and thus are more likely to require mechanical ventilation and/or more intensive clinical care.To obtain an accurate stochastic model that has the ability to detect the severity of lung infection, we develop a second-order Markov-Gibbs random field (MGRF) invariant under rigid transformation (translation or rotation of the image) as well as scale (i.e., pixel size). The parameters of the MGRF model are learned automatically, given a training set of X-ray images with affected lung regions labeled. An X-ray input to the system undergoes pre-processing to correct for non-uniformity of illumination and to delimit the boundary of the lung, using either a fully-automated segmentation routine or manual delineation provided by the radiologist, prior to the diagnosis. The steps of the proposed methodology are: (i) estimate the Gibbs energy at several different radii to describe the inhomogeneity in lung infection; (ii) compute the cumulative distribution function (CDF) as a new representation to describe the local inhomogeneity in the infected region of lung; and (iii) input the CDFs to a new neural network-based fusion system to determine whether the severity of lung infection is low or high. This approach is tested on 200 clinical X-rays from 200 COVID-19 positive patients, 100 of whom died and 100 who recovered using multiple training/testing processes including leave-one-subject-out (LOSO), tenfold, fourfold, and twofold cross-validation tests. The Gibbs energy for lung pathology was estimated at three concentric rings of increasing radii. The accuracy and Dice similarity coefficient (DSC) of the system steadily improved as the radius increased. The overall CAD system combined the estimated Gibbs energy information from all radii and achieved a sensitivity, specificity, accuracy, and DSC of 100%, 97% ± 3%, 98% ± 2%, and 98% ± 2%, respectively, by twofold cross validation. Alternative classification algorithms, including support vector machine, random forest, naive Bayes classifier, K-nearest neighbors, and decision trees all produced inferior results compared to the proposed neural network used in this CAD system. The experiments demonstrate the feasibility of the proposed system as a novel tool to objectively assess disease severity and predict mortality in COVID-19 patients. The proposed tool can assist physicians to determine which patients might require more intensive clinical care, such a mechanical respiratory support.

Cardiac magnetic resonance (MR) imaging is one of the most rigorous form of imaging to assess cardiac function in vivo. Strain analysis allows comprehensive assessment of diastolic myocardial function, which is not indicated by measuring systolic functional parameters using with a normal cine imaging module. Due to the small heart size in mice, it is not possible to perform proper tagged imaging to assess strain. Here, we developed a novel deep learning approach for automated quantification of strain from cardiac cine MR images. Our framework starts by an accurate localization of the LV blood pool center-point using a fully convolutional neural network (FCN) architecture. Then, a region of interest (ROI) that contains the LV is extracted from all heart sections. The extracted ROIs are used for the segmentation of the LV cavity and myocardium via a novel FCN architecture. For strain analysis, we developed a Laplace-based approach to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. Following tracking, the strain estimation is performed using the Lagrangian-based approach. This new automated system for strain analysis was validated by comparing the outcome of these analysis with the tagged MR images from the same mice. There were no significant differences between the strain data obtained from our algorithm using cine compared to tagged MR imaging. Furthermore, we demonstrated that our new algorithm can determine the strain differences between normal and diseased hearts.

Objective: Fontan circulatory inefficiency can be addressed by replacing the missing subpulmonary power source to reverse the Fontan paradox. An implantable cavopulmonary assist device is described that will simultaneously reduce systemic venous pressure and increase pulmonary arterial pressure, improving preload and cardiac output, in a univentricular Fontan circulation on a long-term basis., Methods: A rotary blood pump that was based on the von Karman viscous pump was designed for implantation into the total cavopulmonary connection (TCPC). It will impart modest pressure energy to augment Fontan flow without risk of obstruction. In the event of rotational failure, it is designed to default to a passive flow diverter. Pressure-flow performance was characterized in vitro in a Fontan mock circulatory loop with blood analog., Results: The pump performed through the fully specified operating range, augmenting flow in all 4 directions of the TCPC. Pressure rise of 6 to 8 mm Hg was readily achieved, ranging to 14 mm Hg at highest speed (5600 rpm). Performance was consistent across a wide range of cardiac outputs. In stalled condition (0 rpm), there was no discernible pressure loss across the TCPC., Conclusions: A blood pump technology is described that can reverse the Fontan paradox and may permit a surgical strategy of long-term biventricular maintenance of a univentricular Fontan circulation. The technology is intended for Fontan failure in which right-sided circulatory inefficiencies predominate and ventricular systolic function is preserved. It may also apply before clinical Fontan failure as health maintenance to preempt the progression of Fontan disease., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Ex vivo lung perfusion (EVLP) has the potential to increase the donor pool for lung transplantation by facilitating resuscitation and extended evaluation of marginal organs. Current EVLP methodology employs continuous flow (CF) pumps that produce non-pulsatile EVLP hemodynamics. In this feasibility study, we tested the hypothesis that a pulsatile flow (PF) pump will provide better EVLP support than a CF pump through delivery of physiologic hemodynamics., Methods: Porcine lungs were supported in an EVLP model by centrifugal CF (n = 3) or PF (n = 4) left ventricular assist devices. Lungs were ventilated at 4 to 5 mL/kg, 0.21 fraction of inspired oxygen (FiO2), and perfused with an acellular, albumin-based solution corrected for osmolarity, acid-base balance, and carbon dioxide pressure (≤20 hours at 30°C) for a minimum of 12 hours support. Prostaglandin E1 and 30% albumin were infused continuously. Hemodynamic, respiratory, and blood gas parameters were continuously monitored and digitally recorded hourly. Parenchymal biopsies were used for quantification of wet to dry weight ratio., Results: All lungs maintained function in the EVLP circuit for a minimum of 12 hours (mean 14.7 ± 1 hours) and demonstrated minimal edema formation. The PF EVLP produced higher pulsatility as demonstrated by greater energy equivalent pressure and surplus hemodynamic energy compared with CF EVLP (p < 0.05). There were no statistically significant differences in pulmonary impedance, arterial partial pressure of oxygen/fraction of inspired oxygen, wet to dry weight ratio, and peak airway pressure between CF and PF EVLP., Conclusions: The CF and PF EVLP systems successfully maintained lungs 12+ hours using a modified Steen perfusate (XVIVO Perfusion, Inc, Goteborg, Sweden); however, there were no statistically significant differences between CF and PF groups despite higher pulsatility, suggesting that PF may not offer immediate benefits over CF for prolonged ex vivo lung preservation., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The anatomic and physiologic constraints for pediatric cavopulmonary assist differ markedly from adult Fontan circulations owing to smaller vessel sizes and risk of elevated pulmonary resistance. In this study, hemodynamic and hemolysis performance of a catheter-based viscous impeller pump (VIP) to power the Fontan circulation is assessed at a pediatric scale (∼15 kg) and performance range (0-30 mm Hg)., Methods: Computer simulation and mock circulation studies were conducted to assess the hydraulic performance, acute hemodynamic response to different levels VIP support, and the potential for vena caval collapse. Computational fluid dynamics simulations were used to estimate VIP hydraulic performance, shear rates, and potential for hemolysis. Hemolysis was quantified in a mock loop with fresh bovine blood., Results: A VIP augmented 4-way total cavopulmonary connection flow at pediatric scales and restored systemic pressures and flows to biventricular values, without causing flow obstruction or suction. VIP generated flows up to 4.1 L/min and pressure heads of up to 38 mm Hg at 11,000 rpm. Maximal shear rate was 160 Pa, predicting low hemolysis risk. Observed hemolysis was low with plasma free hemoglobin of 11.4 mg · dL(-1) · h(-1)., Conclusions: A VIP will augment Fontan cavopulmonary flow in the proper pressure and flow ranges, with low hemolysis risk under more stringent pediatric scale and physiology compared with adult scale. This technology may be developed to simultaneously reduce systemic venous pressure and improve cardiac output after stage 2 or 3 Fontan repair. It may serve to compress surgical staging, lessening the pathophysiologic burden of repair., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: An ectopic coronary artery that courses between the aortic root and the pulmonary trunk may lead to sudden cardiac death, especially in athletes. It has been speculated that during exercise, compression of the coronary artery between the great vessels may impair coronary blood flow and produce myocardial ischemia and fatal arrhythmia. However, this hypothesis cannot be tested in humans, and little experimental data exist to explain this phenomenon. To this end, in a calf with an anomalous left coronary artery that coursed from the right sinus of Valsalva between the great vessels, we assessed for myocardial ischemia during pharmacologically induced tachycardia and hypertension., Methods: We identified a juvenile male calf (103 kg) with an anomalous left coronary artery from the right sinus of Valsalva that coursed between the great vessels. Via thoracotomy, the animal was instrumented for hemodynamic measurements. Intravenous dobutamine increased heart rate and myocardial metabolic demands. Intravenous phenylephrine produced arterial hypertension and increased myocardial metabolic demands. Fluorescent-labeled microspheres were used to map regional myocardial blood flow, and hemodynamics were recorded during each condition. Masson's trichrome staining for fibrosis, wheat-germ agglutinin staining for myocyte size, terminal deoxynucleotidyl transferase dUTP nick end-label staining for apoptosis, and isolectin-B4 staining for capillary density were performed., Results: For the first time, empiric data documented that an ectopic coronary artery produced myocardial ischemia during elevated myocardial metabolic demands. Left coronary artery resistance increased in a cardiac cycle-dependent pattern that was consistent with systolic compression between the great vessels. Increased cardiac fibrosis, myocyte hypertrophy, cardiac apoptosis, and capillary density indicated that regional ischemic, inflammatory-mediated myocardial remodeling was present., Conclusions: These findings confirm the proposed mechanism of sudden death and support early surgical repair of coronary arteries that course between the aortic root and the pulmonary trunk., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Acquisition of noncontrast agent cine cardiac magnetic resonance (CMR) gated images through the cardiac cycle is, at present, a well-established part of examining cardiac global function. However, regional quantification is less well established. We propose a new automated framework for analyzing the wall thickness and thickening function on these images that consists of three main steps. First, inner and outer wall borders are segmented from their surrounding tissues with a geometric deformable model guided by a special stochastic speed relationship. The latter accounts for Markov-Gibbs shape and appearance models of the object-of-interest and its background. In the second step, point-to-point correspondences between the inner and outer borders are found by solving the Laplace equation and provide initial estimates of the local wall thickness and the thickening function index. Finally, the effects of the segmentation error is reduced and a continuity analysis of the LV wall thickening is performed through iterative energy minimization using a generalized Gauss-Markov random field (GGMRF) image model. The framework was evaluated on 26 datasets from clinical cine CMR images that have been collected from patients with eleven independent studies, with chronic ischemic heart disease and heart damage. The performance evaluation of the proposed segmentation approach, based on the receiver operating characteristic (ROC) and Dice similarity coefficients (DSC) between manually drawn and automatically segmented contours, confirmed a high robustness and accuracy of the proposed segmentation approach. Furthermore, the Bland-Altman plot is used to assess the limit of agreement of our measurements of the global function parameters compared to the ground truth. Importantly, comparative results on the publicly available database (MICCAI 2009 Cardiac MR Left Ventricle Segmentation) demonstrated a superior performance of the proposed segmentation approach over published methods., (© 2011 IEEE)

Atherosclerotic lesions occur non-randomly at vascular niches in bends and bifurcations where fluid flow can be characterized as "disturbed" (low shear stress with both forward and retrograde flow). Endothelial cells (ECs) at these locations experience significantly lower average shear stress without change in the levels of pressure or strain, which affects the local balance in mechanical stresses. Common in vitro models of atherosclerosis focus primarily on shear stress without accounting for pressure and strain loading. To overcome this limitation, we used our microfluidic endothelial cell culture model (ECCM) to achieve accurate replication of pressure, strain, and shear stress waveforms associated with both normal flow seen in straight sections of arteries and disturbed flow seen in the abdominal aorta in the infrarenal segment at the wall distal to the inferior mesenteric artery (IMA), which is associated with high incidence of atherosclerotic lesion formation. Human aortic endothelial cells (HAECs) were cultured within the ECCM under both normal and disturbed flow and evaluated for cell shape, cytoskeletal alignment, endothelial barrier function, and inflammation using immunofluorescence microscopy and flow cytometry. Results clearly demonstrate quantifiable differences between cells cultured under disturbed flow conditions, which are cuboidal with short and randomly oriented actin microfilaments and show intermittent expression of β-Catenin and cells cultured under normal flow. However, in the absence of pro-inflammatory stimulation, the levels of expression of activation markers: intra cellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), and vascular endothelial cell growth factor - receptor 2 (VEGF-R2) known to be involved in the initiation of plaque formation were only slightly higher in HAECs cultured under disturbed flow in comparison to cells cultured under normal flow.

Background: Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure., Methods: HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated., Results: The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5-6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0-30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs., Conclusions: We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Left ventricular assist devices (LVADs) constitute a recent advance in heart failure (HF) therapeutics. As the rigorous experimental assessment of LVADs in HF requires large animal models, our objective was to develop a bovine model of cardiomyopathy. Male calves (n = 8) were used. Four animals received 1.2 mg/kg intravenous doxorubicin weekly for seven weeks and four separate animals were studied as controls. Doxorubicin-treated animals were followed with weekly echocardiography. Target LV dysfunction was defined as an ejection fraction ≤ 35%. Sixty days after initiating doxorubicin, a terminal study was performed to determine hemodynamic, histological, biochemical, and molecular parameters. All four doxorubicin-treated animals exhibited significant (P < 0.05) contractile dysfunction, with target LV dysfunction achieved in three animals. Doxorubicin-treated hearts exhibited significantly reduced coronary blood flow and interstitial fibrosis and significantly increased apoptosis and myocyte size. Gene expression of atrial natriuretic factor increased more than 3-fold. Plasma norepinephrine and epinephrine levels were significantly increased early and late during the development of cardiomyopathy, respectively. We conclude that sequential administration of intravenous doxorubicin in calves induces a cardiomyopathy with many phenotypic hallmarks of the failing human heart. This clinically-relevant model may be useful for testing pathophysiologic responses to LVADs in the context of HF.

Objective: In a univentricular Fontan circulation, modest augmentation of existing cavopulmonary pressure head (2-5 mm Hg) would reduce systemic venous pressure, increase ventricular filling, and thus substantially improve circulatory status. An ideal means of providing mechanical cavopulmonary support does not exist. We hypothesized that a viscous impeller pump, based on the von Kármán viscous pump principle, is optimal for this role., Methods: A 3-dimensional computational model of the total cavopulmonary connection was created. The impeller was represented as a smooth 2-sided conical actuator disk with rotation in the vena caval axis. Flow was modeled under 3 conditions: (1) passive flow with no disc; (2) passive flow with a nonrotating disk, and (3) induced flow with disc rotation (0-5K rpm). Flow patterns and hydraulic performance were examined for each case. Hydraulic performance for a vaned impeller was assessed by measuring pressure increase and induced flow over 0 to 7K rpm in a laboratory mock loop., Results: A nonrotating actuator disc stabilized cavopulmonary flow, reducing power loss by 88%. Disk rotation (from baseline dynamic flow of 4.4 L/min) resulted in a pressure increase of 0.03 mm Hg. A further increase in pressure of 5 to 20 mm Hg and 0 to 5 L/min flow was obtained with a vaned impeller at 0 to 7K rpm in a laboratory mock loop., Conclusions: A single viscous impeller pump stabilizes and augments cavopulmonary flow in 4 directions, in the desired pressure range, without venous pathway obstruction. A viscous impeller pump applies to the existing staged protocol as a temporary bridge-to-recovery or -transplant in established univentricular Fontan circulations and may enable compressed palliation of single ventricle without the need for intermediary surgical staging or use of a systemic-to-pulmonary arterial shunt., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

An explanation of the mechanisms leading to the beneficial hemodynamic effects of the intra-aortic balloon pump (IABP) is lacking. We hypothesized that inflation and deflation of the balloon would generate a compression (BCW) and an expansion (BEW) wave, respectively, which, when analyzed with wave intensity analysis, could be used to explain the hemodynamic benefits of IABP support. Simultaneous ascending aortic pressure (P(ao)) and flow rate (Q(ao)) were recorded in 25 patients during control conditions and with IABP support of 1:1 and 1:2. Diastolic aortic pressure augmentation (P(aug)) and end-diastolic aortic pressure (ED P(ao)) reduction were calculated from P(ao). Energies of the BCW and BEW were obtained by integrating the wave intensity contour over time. P(aug) was 19.1 mmHg (SD 13.6) during 1:2 support. During 1:1 support significantly higher P(aug) of 21.1 mmHg (SD 13.4) was achieved (P < 0.001). ED P(ao) decreased from 50.9 mmHg (SD 15.1) to 43.9 mmHg (SD 15.7) (P < 0.0001) during 1:1 assistance and the decrease was not statistically different with 1:2. During 1:1 support the energy of BCW was correlated positively to P(aug) (r = 0.83, P < 0.0001) and energy of the BEW correlated negatively to ED P(ao) (r = 0.78, P < 0.005); these relationships were not statistically different during 1:2. In conclusion, the energies of the BCW and BEW are directly related to P(aug) and ED P(ao), which are the conventional hemodynamic parameters indicating IABP benefits. These findings imply a cause and effect mechanism between the energies of BCW and BEW, and IABP hemodynamic effects.

Objective: We sought to investigate differences in indices of pulsatility between patients with normal ventricular function and patients with heart failure studied at the time of implantation with continuous-flow or pulsatile-flow left ventricular assist devices., Methods: Eight patients with normal ventricular function and 22 patients with heart failure were studied. A high-fidelity aortic and left ventricular pressure catheter was inserted retrograde through the aortic valve into the left ventricle, and transit-time flow probes were placed on the aorta and device outflow graft. Hemodynamic waveforms were recorded at native heart rate before cardiopulmonary bypass and over a range of device flow rates controlled by adjusting beat rate or rpm. These data were used to calculate vascular input impedance and 2 indices of vascular pulsatility: energy-equivalent pressure and surplus hemodynamic energy., Results: At low support levels, pulsatile support restored surplus hemodynamic energy to within 2.5% of normal values, whereas continuous support diminished surplus energy by more than 93%. At high support levels, pulsatile support augmented surplus energy by 49% over normal values, whereas continuous support further diminished surplus energy by 97%. Pulsatile support diminished vascular impedance from baseline failure values, whereas continuous support increased impedance. Vascular impedances at baseline for patients undergoing pulsatile and continuous support and during pulsatile support revealed normal vascular compliance, whereas impedance during continuous support indicated a loss of compliance (or "stiffening") of the vasculature., Conclusion: These results suggest that selection of device type and flow rate can influence vascular pulsatility and input impedance, which might affect clinical outcomes.