Magnetic Resonance Imaging Based Flow Field and Lagrangian Particle Tracking From a Left Ventricular Assist Device.

This study explores the optimal left ventricular assist device (LVAD) cannula outflow configuration in a patient-specific replica of the aorta. The volumetric velocity field is measured using phase-contrast magnetic resonance imaging (PC-MRI) under a physiologically relevant steady flow. The effect of the LVAD outflow graft insertion site and anastomosis angle on the transport of embolic particles to cranial vessels is studied by solving the particle equation of motion for spheres in the range of 0.1-1.0 mm using the measured three-dimensional (3D) velocity field. Results show that for a given aorta anatomy, it is possible to design the cannula graft location and terminal curvature so that the probability of embolic transport to the cranial vessels is significantly minimized. This is particularly important since the complex flow pattern in each cannula case affects the embolic trajectories differently, and hence the common assumption that particles distribute by the volumetric flow division does not hold.

Real World Characterization of Chronic Pain, Success Rates and Implant Rates: Evidence from a Digital Health Platform of Patients Undergoing Spinal Cord Stimulation Evaluations.

Spinal cord stimulation is an effective treatment for those experiencing chronic back and leg pain but requires a temporary evaluation period (SCSeval) before permanent implantation. We present real-world data from 7,000 patients who underwent SCSeval while utilizing a mobile digital health platform for education, feedback, and outcomes collection during their surgical journey. We analyzed preoperative patient demographics, characterized patient pain profiles using the patient-reported outcomes measurement information system-29 surveys, and calculated the rates of conversion from temporary to permanent spinal cord stimulation (SCS) implantation. Between August 1, 2021, and March 2, 2023, 7,000 patients (mean age 59.1, 59.6% female) underwent SCSeval procedures while utilizing a mobile application. Patients commonly experienced aching, sharp, stabbing, tingling, numb, and burning pain. Patients had tried multiple prior therapies and wanted to reduce their use of opioids and pain medications. Overall, 90.1% of the patients had a successful SCSeval, and 80.4% of those converted to permanent implant, with the highest rates among those who underwent SCSeval in a hospital setting. There was a significant improvement in all domains of pain as evaluated by pre and postoperative patient-reported outcomes measurement information system-29 surveys. This study supports the use of digital health technology as part of the SCS journey to improve the patient experience and allow for robust patient-reported outcomes collection. The overall rate of SCSeval to permanent SCS in our study of 72.4% was higher than national rates of 64%, suggesting that an app may allow clinicians to better quantify changes in chronic pain and provide more insight into choosing to implant SCS permanently. PERSPECTIVE: This article presents real-world evidence from a digital health platform for therapy education and outcomes collection from patients undergoing spinal cord stimulation evaluation procedures. Such tools could allow for better pain characterization and allow for more nuanced tracking of patient outcomes among those with chronic pain.

Flow residence time in intracranial aneurysms evaluated by in vitro 4D flow MRI.

The process of an intracranial aneurysm development, growth, and rupture is multifaceted and complex. In addition, clinical observations have identified the potential of thrombus formation within such aneurysms. While the underlying mechanism is not fully understood, the thrombi represent a potential risk factor for ischemic stroke. Emerging studies indicate that blood residence time (RT) is a promising hemodynamic metric associated with the aneurysm rupture and formation of intra-aneurysmal thrombi. Here, we present a methodology to experimentally evaluate both trajectory-wise and local RT based on magnetic resonance imaging (MRI) velocimetry, and apply it to in vitro flow measurements in scaled-up replicas of 9 patient-specific intracranial aneurysms. Lagrangian tracks of massless tracers are integrated from the velocity fields and averaged to return the mean RT in the aneurysm sac. This is found to be closely approximated by a simple time scale based on the sac diameter and space-time average of the aneurysmal fluid velocity. The mean RT is also correlated with the inflow time scale at the parent artery. These results also provide a basis for the estimation of RT when high-resolution hemodynamic maps are not available. With the continuous increase in accuracy and resolution enabled by progress in MRI technology, the methodology described here may in the future be applicable to in vivo data.

Conceptual Framework Development for a Double-Walled Aortic Stent-Graft to Manage Blood Pressure.

A double-walled stent-graft (DWSG) design with a compressible gas layer was conceived with the goal of treating hypertension in patients receiving an aortic stent-graft. Early prototypes were developed to evaluate the design concept through static measurements from a finite element (FE) model and quasi-static inflation experiments, and through dynamic measurements from an in vitro flow loop and the three-element Windkessel model. The amount of gas in the gas layer and the properties of the flexible inner wall were the primary variables evaluated in this study. Properties of the inner wall had minimal effect on DWSG behavior, but increased gas charge led to increased fluid capacitance and larger reduction in peak and pulse pressures. In the flow loop, placement of the DWSG decreased pulse pressure by over 20% compared to a rigid stent-graft. Capacitance measurements were consistent across all methods, with the maximum capacitance estimated at 0.07 mL/mmHg for the largest gas charge in the 15 cm long prototype. Windkessel model predictions for in vivo performance of a DWSG placed in the aorta of a hypertensive patient showed pulse pressure reduction of 14% compared to a rigid stent-graft case, but pressures never returned to unstented values. These results indicate that the DWSG design has potential to be developed into a new treatment for hypertensive patients requiring an aortic intervention.

Particle transport and deposition correlation with near-wall flow characteristic under inspiratory airflow in lung airways.

Exposure of lung airways to detrimental suspended aerosols in the environment increases the vulnerability of the respiratory and cardiovascular systems. In addition, recent developments in therapeutic inhalation devices magnify the importance of particle transport. In this manuscript, particle transport and deposition patterns in the upper tracheobronchial (TB) tree were studied where the inertial forces are considerable for microparticles. Wall shear stress divergence (WSSdiv) is proposed as a wall-based parameter that can predict particle deposition patterns. WSSdiv is proportional to near-wall normal velocity and can quantify the strength of flow towards and away from the wall. Computational fluid dynamics (CFD) simulations were performed to quantify airflow velocity and WSS vectors for steady inhalation in one case-control and unsteady inhalation in six subject-specific airway trees. Turbulent flow simulation was performed for the steady case using large eddy simulation to study the effect of turbulence. Magnetic resonance velocimetry (MRV) measurements were used to validate the case-control CFD simulation. Inertial particle transport was modeled by solving the Maxey-Riley equation in a Lagrangian framework. Deposition percentage (DP) was quantified for the case-control model over five particle sizes. DP was found to be proportional to particle size in agreement with previous studies in the literature. A normalized deposition concentration (DC) was defined to characterize localized deposition. A relatively strong correlation (Pearson value > 0.7) was found between DC and positive WSSdiv for physiologically relevant Stokes (St) numbers. Additionally, a regional analysis was performed after dividing the lungs into smaller areas. A spatial integral of positive WSSdiv over each division was shown to maintain a very strong correlation (Pearson value > 0.9) with cumulative spatial DC or regional dosimetry. The conclusions were generalized to a larger population in which two healthy and four asthmatic patients were investigated. This study shows that WSSdiv could be used to predict the qualitative surface deposition and relative regional dosimetry without the need to solve a particle transport problem.

Ventilation-induced jet suggests biotrauma in reconstructed airways of the intubated neonate.

We investigate respiratory flow phenomena in a reconstructed upper airway model of an intubated neonate undergoing invasive mechanical ventilation, spanning conventional to high-frequency ventilation (HFV) modes. Using high-speed tomographic particle image velocimetry, we resolve transient, three-dimensional flow fields and observe a persistent jet flow exiting the endotracheal tube whose strength is directly modulated according to the ventilation protocol. We identify this synthetic jet as the dominating signature of convective flow under intubated ventilation. Concurrently, our in silico wall shear stress analysis reveals a hitherto overlooked source of ventilator-induced lung injury as a result of jet impingement on the tracheal carina, suggesting damage to the bronchial epithelium; this type of injury is known as biotrauma. We find HFV advantageous in mitigating the intensity of such impingement, which may contribute to its role as a lung protective method. Our findings may encourage the adoption of less invasive ventilation procedures currently used in neonatal intensive care units.

In Vitro Study of Particle Transport in Successively Bifurcating Vessels.

To reach a predictive understanding of how particles travel through bifurcating vessels is of paramount importance in many biomedical settings, including embolization, thromboembolism, and drug delivery. Here we utilize an in vitro model in which solid particles are injected through a rigid vessel that symmetrically bifurcates in successive branching generations. The geometric proportion and fluid dynamics parameters are relevant to the liver embolization. The volumetric flow field is reconstructed via phase-contrast magnetic resonance imaging, from which the particle trajectories are calculated for a range of size and density using the particle equation of motion. The method is validated by directly tracking the injected particles via optical imaging. The results indicate that, opposite to the common assumption, the particles distribution is fundamentally different from the volumetric flow partition. In fact, the amount of delivered particles vary substantially between adjacent branches even when the flow is uniformly distributed. This is not due to the inertia of the particles, nor to gravity. The particle distribution is rather rooted in their different pathways, which in turn are linked to their release origin along the main vessel cross-section. Therefore, the tree geometry and the associated flow streamlines are the prime determinant of the particle fate, while local changes of volumetric flow rate to selected branches do not generally produce proportional changes of particle delivery.

Topological analysis of particle transport in lung airways: Predicting particle source and destination.

Particle transport in lung airways can induce respiratory disease and play a vital role in aerosol drug delivery. Herein, we present dynamical systems features that influence airflow and particle transport in the tracheobronchial trees. Computational fluid dynamics (CFD) was used to solve for unsteady airflow in a patient-specific model. Particle tracking simulations were performed for micron-size particles. The destination map that connects the particle final location to the initial location and injection time was constructed. Finite-time Lyapunov exponent (FTLE) fields were calculated to identify inertial Lagrangian coherent structures (ILCS), topological features that act as separatrices. Our results demonstrated that these topological features control the destination map at the trachea. The temporal evolution of ILCS influenced the sensitivity of particle transport fate to injection time, whereas the emergence of new ILCS with an increased integration time controlled transport to different generations of airways. Additionally, particles starting at the ILCS were shown to mostly deposit at the airway walls. Finally, an innovative source inversion strategy was introduced to integrate the Maxey-Riley equation backward in time and identify the origin of dispersed particles. Our study explores novel dynamical systems tools that improve our understanding of particle transport and deposition in the airways and could be used to guide future targeted drug delivery studies.

Airway morphology and inspiratory flow features in the early stages of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is among the leading causes of death worldwide. Inhaled pollutants are the prime risk factor, but the pathogenesis and progression of the diseased is poorly understood. Most studies on the disease onset and trajectory have focused on genetic and molecular biomarkers. Here we investigate the role of the airway anatomy and the consequent respiratory fluid mechanics on the development of COPD. METHODS: We segmented CT scans from a five-year longitudinal study in three groups of smokers (18 subjects each) having: (i) minimal/mild obstruction at baseline with declining lung function at year five; (ii) minimal/mild obstruction at baseline with stable function, and (iii) normal and stable lung function over the five year period. We reconstructed the bronchial trees up to the 7th generation, and for one subject in each group we performed MRI velocimetry in 3D printed models. FINDINGS: The subjects with airflow obstruction at baseline have smaller airway diameters, smaller child-to-parent diameter ratios, larger length-to-diameter ratios, and smaller fractal dimensions. The differences are more significant for subjects that develop severe decline in pulmonary function. The secondary flows that characterize lateral dispersion along the airways are found to be less intense in the subjects with airflow obstruction. INTERPRETATION: These results indicate that morphology of the conducting airways and inspiratory flow features are correlated with the status and progression of COPD already at an early stage of the disease. This suggests that imaging-based biomarkers may allow a pre-symptomatic diagnosis of disease progression.

Morphological and functional properties of the conducting human airways investigated by in vivo computed tomography and in vitro MRI.

The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyzed CT scans of a cohort of healthy subjects and obtained comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle. Although some of the geometric parameters (such as the child-to-parent branch diameter ratio) are found to be in line with accepted values, for others (such as the branch length-to-diameter ratio) our findings challenge the common assumptions. We also evaluated several metrics of self-similarity, including the fractal dimension of the airway tree. Additionally, we used phase-contrast magnetic resonance imaging (MRI) to obtain the volumetric flow field in the three-dimensional-printed airway model of one of the subjects during steady inhalation. This is used to relate structural and functional parameters and, in particular, to close the power-law relationship between branch flow rate and diameter. The diameter exponent is found to be significantly lower than in the usually assumed Poiseuille regime, which we attribute to the strong secondary (i.e., transverse) velocity component. The strength of the secondary velocity with respect to the axial component exceeds the levels found in idealized airway models and persists within the first seven generations. NEW & NOTEWORTHY We performed a comprehensive computed tomography-based study of the conductive airway morphology in normal human subjects, including branch diameter, length, and mutual angles. We found significant departure from classic homothetic relationships. We also carried out MRI measurements of the three-dimensional inspiratory flow in an anatomy-based model and directly assessed structure-function relationships that have so far been assumed. We found that strong secondary flows (i.e., transverse velocity components) persist through the first seven generations of bronchial branching.

Hemodynamics in a giant intracranial aneurysm characterized by in vitro 4D flow MRI.

Experimental and computational data suggest that hemodynamics play a critical role in the development, growth, and rupture of cerebral aneurysms. The flow structure, especially in aneurysms with a large sac, is highly complex and three-dimensional. Therefore, volumetric and time-resolved measurements of the flow properties are crucial to fully characterize the hemodynamics. In this study, phase-contrast Magnetic Resonance Imaging is used to assess the fluid dynamics inside a 3D-printed replica of a giant intracranial aneurysm, whose hemodynamics was previously simulated by multiple research groups. The physiological inflow waveform is imposed in a flow circuit with realistic cardiovascular impedance. Measurements are acquired with sub-millimeter spatial resolution for 16 time steps over a cardiac cycle, allowing for the detailed reconstruction of the flow evolution. Moreover, the three-dimensional and time-resolved pressure distribution is calculated from the velocity field by integrating the fluid dynamics equations, and is validated against differential pressure measurements using precision transducers. The flow structure is characterized by vortical motions that persist within the aneurysm sac for most of the cardiac cycle. All the main flow statistics including velocity, vorticity, pressure, and wall shear stress suggest that the flow pattern is dictated by the aneurysm morphology and is largely independent of the pulsatility of the inflow, at least for the flow regimes investigated here. Comparisons are carried out with previous computational simulations that used the same geometry and inflow conditions, both in terms of cycle-averaged and systolic quantities.