Real-time quantification of in vivo cerebrospinal fluid velocity using the functional magnetic resonance imaging inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory-gated approaches, such as 4D flow magnetic resonance imaging (MRI), cannot capture CSF movement in real time because of limited temporal resolution and, in addition, deteriorate in accuracy at low fluid velocities. Other techniques like real-time phase-contrast-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability, even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional MRI (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath-holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Comparative Assessment of Biomechanical Parameters in Subjects With Multiple Cerebral Aneurysms Using Fluid-Structure Interaction Simulations.

Cerebral aneurysm progression is a result of a complex interplay of the biomechanical and clinical risk factors that drive aneurysmal growth and rupture. Subjects with multiple aneurysms are unique cases wherein clinical risk factors are expected to affect each aneurysm equally, thus allowing for disentangling the effect of biomechanical factors on aneurysmal growth. Toward this end, we performed a comparative computational fluid-structure interaction analysis of aneurysmal biomechanics in image-based models of stable and growing aneurysms in the same subjects, using the cardiovascular simulation platform simvascular. We observed that areas exposed to low shear and the median peak systolic arterial wall displacement were higher by factors of 2 or more and 1.5, respectively, in growing aneurysms as compared to stable aneurysms. Furthermore, we defined a novel metric, the oscillatory stress index (OStI), which indicates locations of oscillating arterial wall stresses. We observed that growing aneurysms were characterized by regions of combined low wall shear and high OStI, which we hypothesize to be associated with regions of collagen degradation and remodeling. Such regions were either absent or below 5% of the surface area in stable aneurysms. Our results lay the groundwork for future studies in larger cohorts of subjects, to evaluate the statistical significance of these biomechanical parameters in cerebral aneurysm growth.

Accelerated dual-venc 4D flow MRI with variable high-venc spatial resolution for neurovascular applications.

PURPOSE: Dual-velocity encoded (dual-venc or DV) 4D flow MRI achieves wide velocity dynamic range and velocity-to-noise ratio (VNR), enabling accurate neurovascular flow characterization. To reduce scan time, we present interleaved dual-venc 4D Flow with independently prescribed, prospectively undersampled spatial resolution of the high-venc (HV) acquisition: Variable Spatial Resolution Dual Venc (VSRDV). METHODS: A prototype VSRDV sequence was developed based on a Cartesian acquisition with eight-point phase encoding, combining PEAK-GRAPPA acceleration with zero-filling in phase and partition directions for HV. The VSRDV approach was optimized by varying z, the zero-filling fraction of HV relative to low-venc, between 0%-80% in vitro (realistic neurovascular model with pulsatile flow) and in vivo (n = 10 volunteers). Antialiasing precision, mean and peak velocity quantification accuracy, and test-retest reproducibility were assessed relative to reference images with equal-resolution HV and low venc (z = 0%). RESULTS: In vitro results for all z demonstrated an antialiasing true positive rate at least 95% for RPEAK-GRAPPA$$ {R}_{\mathrm{PEAK}-\mathrm{GRAPPA}} $$  = 2 and 5, with no linear relationship to z (p = 0.62 and 0.13, respectively). Bland-Altman analysis for z = 20%, 40%, 60%, or 80% versus z = 0% in vitro and in vivo demonstrated no bias >1% of venc in mean or peak velocity values at any RZF$$ {R}_{\mathrm{ZF}} $$ . In vitro mean and peak velocity, and in vivo peak velocity, had limits of agreement within 15%. CONCLUSION: VSRDV allows up to 34.8% scan time reduction compared to PEAK-GRAPPA accelerated DV 4D Flow MRI, enabling large spatial coverage and dynamic range while maintaining VNR and velocity measurement accuracy.

Hemodynamics of Cerebral Aneurysms: Connecting Medical Imaging and Biomechanical Analysis.

In the last two decades, numerous studies have conducted patient-specific computations of blood flow dynamics in cerebral aneurysms and reported correlations between various hemodynamic metrics and aneurysmal disease progression or treatment outcomes. Nevertheless, intra-aneurysmal flow analysis has not been adopted in current clinical practice, and hemodynamic factors usually are not considered in clinical decision making. This review presents the state of the art in cerebral aneurysm imaging and image-based modeling, discussing the advantages and limitations of each approach and focusing on the translational value of hemodynamic analysis. Combining imaging and modeling data obtained from different flow modalities can improve the accuracy and fidelity of resulting velocity fields and flow-derived factors that are thought to affect aneurysmal disease progression. It is expected that predictive models utilizing hemodynamic factors in combination with patient medical history and morphological data will outperform current risk scores and treatment guidelines. Possible future directions include novel approaches enabling data assimilation and multimodality analysis of cerebral aneurysm hemodynamics.

Integrated Image-Based Computational Fluid Dynamics Modeling Software as an Instructional Tool.

Computational modeling of cardiovascular flows is becoming increasingly important in a range of biomedical applications, and understanding the fundamentals of computational modeling is important for engineering students. In addition to their purpose as research tools, integrated image-based computational fluid dynamics (CFD) platforms can be used to teach the fundamental principles involved in computational modeling and generate interest in studying cardiovascular disease. We report the results of a study performed at five institutions designed to investigate the effectiveness of an integrated modeling platform as an instructional tool and describe "best practices" for using an integrated modeling platform in the classroom. Use of an integrated modeling platform as an instructional tool in nontraditional educational settings (workshops, study abroad programs, in outreach) is also discussed. Results of the study show statistically significant improvements in understanding after using the integrated modeling platform, suggesting such platforms can be effective tools for teaching fundamental cardiovascular computational modeling principles.

Cerebral circulation time derived from fMRI signals in large blood vessels.

BACKGROUND: The systemic low-frequency oscillation (sLFO) functional (f)MRI signals extracted from the internal carotid artery (ICA) and the superior sagittal sinus (SSS) are found to have valuable physiological information. PURPOSE: 1) To further develop and validate a method utilizing these signals to measure the delay times from the ICAs and the SSS. 2) To establish the delay time as an effective perfusion biomarker that associates with cerebral circulation time (CCT). 3) To explore within subject variations, and the effects of gender and age on the delay times. STUDY TYPE: Prospective. SUBJECTS: In all, 100 healthy adults (Human Connectome Project [HCP], age range 22-36 years, 54 females and 46 males), 56 healthy children (Adolescent Brain Cognitive Development project) were included. FIELD STRENGTH/SEQUENCE: Echo planar imaging (EPI) sequence at 3T. ASSESSMENT: The sLFO fMRI signals from the ICAs and the SSSs were extracted from the resting state fMRI data. The maximum cross-correlation coefficients and their corresponding delay times were calculated. The gender and age differences of delay times were assessed statistically. STATISTICAL TESTS: T-tests were conducted to measure the gender differences. The Kruskal-Wallis test was used to detect age differences. RESULTS: Consistent and robust results were found from 80% of the 400 HCP scans included. Negative correlations (-0.67) between the ICA and the SSS signals were found with the ICA signal leading the SSS signal by ∼5 sec. Within subject variation was 2.23 sec at the 5% significance level. The delay times were not significantly different between genders (P = 0.9846, P = 0.2288 for the left and right ICA, respectively). Significantly shorter delay times (4.3 sec) were found in the children than in the adults (P < 0.01). DATA CONCLUSION: We have shown that meaningful perfusion information (ie, CCT) can be derived from the sLFO fMRI signals of the large blood vessels. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1504-1513.

A workflow for viewing biomedical computational fluid dynamics results and corresponding data within virtual and augmented reality environments.

Researchers conducting computational fluid dynamics (CFD) modeling can spend weeks obtaining imaging data, determining boundary conditions, running simulations and post-processing files. However, results are typically viewed on a 2D display and often at one point in time thus reducing the dynamic and inherently three-dimensional data to a static image. Results from different pathologic states or cases are rarely compared in real-time, and supplementary data are seldom included. Therefore, only a fraction of CFD results are typically studied in detail, and associations between mechanical stimuli and biological response may be overlooked. Virtual and augmented reality facilitate stereoscopic viewing that may foster extraction of more information from CFD results by taking advantage of improved depth cues, as well as custom content development and interactivity, all within an immersive approach. Our objective was to develop a straightforward, semi-automated workflow for enhanced viewing of CFD results and associated data in an immersive virtual environment (IVE). The workflow supports common CFD software and has been successfully completed by novice users in about an hour, demonstrating its ease of use. Moreover, its utility is demonstrated across clinical research areas and IVE platforms spanning a range of cost and development considerations. We are optimistic that this advancement, which decreases and simplifies the steps to facilitate more widespread use of immersive CFD viewing, will foster more efficient collaboration between engineers and clinicians. Initial clinical feedback is presented, and instructional videos, manuals, templates and sample data are provided online to facilitate adoption by the community.

Automatic 4D Flow MRI Segmentation Using the Standardized Difference of Means Velocity.

We present a method to automatically segment 4D flow magnetic resonance imaging (MRI) by identifying net flow effects using the standardized difference of means (SDM) velocity. The SDM velocity quantifies the ratio between the net flow and observed flow pulsatility in each voxel. Vessel segmentation is performed using an F-test, identifying voxels with significantly higher SDM velocity values than background voxels. We compare the SDM segmentation algorithm against pseudo-complex difference (PCD) intensity segmentation of 4D flow measurements in in vitro cerebral aneurysm models and 10 in vitro Circle of Willis (CoW) datasets. We also compared the SDM algorithm to convolutional neural network (CNN) segmentation in 5 thoracic vasculature datasets. The in vitro flow phantom geometry is known, while the ground truth geometries for the CoW and thoracic aortas are derived from high-resolution time-of-flight (TOF) magnetic resonance angiography and manual segmentation, respectively. The SDM algorithm demonstrates greater robustness than PCD and CNN approaches and can be applied to 4D flow data from other vascular territories. The SDM to PCD comparison demonstrated an approximate 48% increase in sensitivity in vitro and 70% increase in the CoW, respectively; the SDM and CNN sensitivities were similar. The vessel surface derived from the SDM method was 46% closer to the in vitro surfaces and 72% closer to the in vitro TOF surfaces than the PCD approach. The SDM and CNN approaches both accurately identify vessel surfaces. The SDM algorithm is a repeatable segmentation method, enabling reliable computation of hemodynamic metrics associated with cardiovascular disease.

Real-time Quantification of in vivo cerebrospinal fluid velocity using fMRI inflow effect.

In vivo estimation of cerebrospinal fluid (CSF) velocity is crucial for understanding the glymphatic system and its potential role in neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Current cardiac or respiratory gated approaches, such as 4D flow MRI, cannot capture CSF movement in real time due to limited temporal resolution and in addition deteriorate in accuracy at low fluid velocities. Other techniques like real-time PC-MRI or time-spatial labeling inversion pulse are not limited by temporal averaging but have limited availability even in research settings. This study aims to quantify the inflow effect of dynamic CSF motion on functional magnetic resonance imaging (fMRI) for in vivo, real-time measurement of CSF flow velocity. We considered linear and nonlinear models of velocity waveforms and empirically fit them to fMRI data from a controlled flow experiment. To assess the utility of this methodology in human data, CSF flow velocities were computed from fMRI data acquired in eight healthy volunteers. Breath holding regimens were used to amplify CSF flow oscillations. Our experimental flow study revealed that CSF velocity is nonlinearly related to inflow effect-mediated signal increase and well estimated using an extension of a previous nonlinear framework. Using this relationship, we recovered velocity from in vivo fMRI signal, demonstrating the potential of our approach for estimating CSF flow velocity in the human brain. This novel method could serve as an alternative approach to quantifying slow flow velocities in real time, such as CSF flow in the ventricular system, thereby providing valuable insights into the glymphatic system's function and its implications for neurological disorders.

Imaging and modeling of flow in porous media using clinical nuclear emission tomography systems and computational fluid dynamics.

This paper presents experimental and modeling aspects of applying nuclear emission tomography to study fluid flow in laboratory packed porous media columns of the type frequently used in geophysics, geochemistry and hydrology research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive tracer concentrations. Dynamic sequences obtained using 18F-FDG PET are used to trace flow through a 5 cm diameter × 20 cm tall sand packed column with and without an impermeable obstacle. In addition, a custom-made rotating column setup placed in a clinical two-headed SPECT camera is used to image 99mTc-DTPA tracer propagation in a through-flowing column (10 cm diameter × 30 cm tall) packed with recovered aquifer sediments. A computational fluid dynamics software package FLUENT is used to model the observed flow dynamics. Tracer distributions obtained in the simulations in the smaller column uniformly packed with sand and in the column with an obstacle are remarkably similar to the reconstructed images in the PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for the larger column slurry-packed with sub-surface sediment and slow upward flow. In the numerical simulation of the SPECT study, two symmetric channels with increased permeability are prescribed along the column walls, which result in the emergence of two well-defined preferential flow paths. Methods and results of this work provide new opportunities in hydrologic and biogeochemical research. The primary target application for developed technologies is non-destructive, non-perturbing, quantitative imaging of flow dynamics within laboratory scale porous media systems.

A multi-modality approach for enhancing 4D flow magnetic resonance imaging via sparse representation.

This work evaluates and applies a multi-modality approach to enhance blood flow measurements and haemodynamic analysis with phase-contrast magnetic resonance imaging (4D flow MRI) in cerebral aneurysms (CAs). Using a library of high-resolution velocity fields from patient-specific computational fluid dynamic simulations and in vitro particle tracking velocimetry measurements, the flow field of 4D flow MRI data is reconstructed as the sparse representation of the library. The method was evaluated with synthetic 4D flow MRI data in two CAs. The reconstruction enhanced the spatial resolution and velocity accuracy of the synthetic MRI data, leading to reliable pressure and wall shear stress (WSS) evaluation. The method was applied on in vivo 4D flow MRI data acquired in the same CAs. The reconstruction increased the velocity and WSS by 6-13% and 39-61%, respectively, suggesting that the accuracy of these quantities was improved since the raw MRI data underestimated the velocity and WSS by 10-20% and 40-50%, respectively. The computed pressure fields from the reconstructed data were consistent with the observed flow structures. The results suggest that using the sparse representation flow reconstruction with in vivo 4D flow MRI enhances blood flow measurement and haemodynamic analysis.

Wall Shear Stress Estimation for 4D Flow MRI Using Navier-Stokes Equation Correction.

This study introduces a novel wall shear stress (WSS) estimation method for 4D flow MRI. The method improves the WSS accuracy by using the reconstructed pressure gradient and the flow-physics constraints to correct velocity gradient estimation. The method was tested on synthetic 4D flow data of analytical Womersley flow and flow in cerebral aneurysms and applied to in vivo 4D flow data acquired in cerebral aneurysms and aortas. The proposed method's performance was compared to the state-of-the-art method based on smooth-spline fitting of velocity profile and the WSS calculated from uncorrected velocity gradient. The proposed method improved the WSS accuracy by as much as 100% for the Womersley flow and reduced the underestimation of mean WSS by 39 to 50% for the synthetic aneurysmal flow. The predicted mean WSS from the in vivo aneurysmal data using the proposed method was 31 to 50% higher than the other methods. The predicted aortic WSS using the proposed method was 3 to 6 times higher than the other methods and was consistent with previous CFD studies and the results from recently developed methods that take into account the limited spatial resolution of 4D flow MRI. The proposed method improves the accuracy of WSS estimation from 4D flow MRI, which can help predict blood vessel remodeling and progression of cardiovascular diseases.

Modeling Bias Error in 4D Flow MRI Velocity Measurements.

We present a model to estimate the bias error of 4D flow magnetic resonance imaging (MRI) velocity measurements. The local instantaneous bias error is defined as the difference between the expectation of the voxel's measured velocity and actual velocity at the voxel center. The model accounts for bias error introduced by the intra-voxel velocity distribution and partial volume (PV) effects. We assess the intra-voxel velocity distribution using a 3D Taylor Series expansion. PV effects and numerical errors are considered using a Richardson extrapolation. The model is applied to synthetic Womersley flow and in vitro and in vivo 4D flow MRI measurements in a cerebral aneurysm. The bias error model is valid for measurements with at least 3.75 voxels across the vessel diameter and signal-to-noise ratio greater than 5. All test cases exceeded this diameter to voxel size ratio with diameters, isotropic voxel sizes, and velocity ranging from 3-15mm, 0.5-1mm, and 0-60cm/s, respectively. The model accurately estimates the bias error in voxels not affected by PV effects. In PV voxels, the bias error is an order of magnitude higher, and the accuracy of the bias error estimation in PV voxels ranges from 67.3% to 108% relative to the actual bias error. The bias error estimated for in vivo measurements increased two-fold at systole compared to diastole in partial volume and non-partial volume voxels, suggesting the bias error varies over the cardiac cycle. This bias error model quantifies 4D flow MRI measurement accuracy and can help plan 4D flow MRI scans.

Challenges in Modeling Hemodynamics in Cerebral Aneurysms Related to Arteriovenous Malformations.

PURPOSE: The significantly higher incidence of aneurysms in patients with arteriovenous malformations (AVMs) suggests a strong hemodynamic relationship between these lesions. The presence of an AVM alters hemodynamics in proximal vessels by drastically changing the distal resistance, thus affecting intra-aneurysmal flow. This study discusses the challenges associated with patient-specific modeling of aneurysms in the presence of AVMs. METHODS: We explore how the presence of a generic distal AVM affects upstream aneurysms by examining the relationship between distal resistance and aneurysmal wall shear stress using physiologically realistic estimates for the influence of the AVM on hemodynamics. Using image-based computational models of aneurysms and surrounding vasculature, aneurysmal wall-shear stress is calculated for a range of distal resistances corresponding to the presence of AVMs of various sizes and compared with a control case representing the absence of an AVM. RESULTS: In the patient cases considered, the alteration in aneurysmal wall shear stress due to the presence of an AVM is considerable, as much as 19 times the base case wall shear stress. Furthermore, the relationship between aneurysmal wall shear stress and distal resistance is shown to be highly geometry-dependent and nonlinear. In most cases, the range of physiologically realistic possibilities for AVM-related distal resistance are so large that patient-specific flow measurements are necessary for meaningful predictions of wall shear stress. CONCLUSIONS: The presented work offers insight on the impact of distal AVMs on aneurysmal wall shear stress using physiologically realistic computational models. Patient-specific modeling of hemodynamics in aneurysms and associated AVMs has great potential for understanding lesion pathogenesis, surgical planning, and assessing the effect of treatment of one lesion relative to another. However, we show that modeling approaches cannot usually meaningfully quantify the impact of AVMs if based solely on imaging data from CT and X-ray angiography, currently used in clinical practice. Based on recent studies, it appears that 4D flow MRI is one promising approach to obtaining meaningful patient-specific flow boundary conditions that improve modeling fidelity.

Temporal stability of dysmorphic fusiform aneurysms of the intracranial internal carotid artery.

PURPOSE: Estimation of the stability of dysmorphic fusiform aneurysms of the intracranial internal carotid artery requires precise monitoring of their volumes. This report describes a method of magnetic resonance (MR) imaging and three-dimensional postprocessing to study the evolution of these aneurysms in a prospective cohort of patients not immediately suitable for surgery or endovascular treatment. MATERIALS AND METHODS: Ten patients with fusiform aneurysms of the intracranial internal carotid artery underwent serial MR studies. Five patients were studied at two time points and the remainder at multiple time points (mean delay between studies, 12.6 mo ± 3.8). For each patient, studies from all time points were coregistered. The volumes of each vessel component were calculated. RESULTS: Mean aneurysm volume was 833 mm(3) ± 878. Mean annual rate of volume progression was 1.37% ± 2.09. All aneurysms were thrombus-free. CONCLUSIONS: This study indicates that, given the relatively low rate of progression of dysplastic fusiform aneurysms and the complexity of their shape, three-dimensional quantitative volumetric methods can be helpful in monitoring whether any growth has occurred.

Advanced vascular imaging techniques.

This chapter outlines recent advances in imaging of disorders of the cervicocerebral vasculature that permit evaluation of the lumen, the vessel wall, and the patterns of blood flow within the vessel. Noninvasive MR techniques to evaluate the vessel lumen, such as noncontrast time-of-flight magnetic resonance angiography and contrast-enhanced magnetic resonance angiography (CEMRA) are routinely used in diagnosis, planning, and posttreatment follow-up. More recently, high-resolution vessel wall imaging MRI (VWMRI) has been developed, which provides additional information about the vessel wall or aneurysm wall. VWMRI wall signal and enhancement patterns may permit differentiation between vasculopathies and between stable and unstable unruptured aneurysms. In addition, the study of blood flow patterns using phase-contrast MRI (4D flow MRI) and image-based computational fluid dynamics has been used to characterize flow and wall shear stress within aneurysms, flow within arteriovenous malformations (AVMs) and pulsatile tinnitus. Digital subtraction angiography (DSA), however, remains the gold standard in the evaluation and treatment of neurovascular diseases. New adjunctive DSA techniques, such as 4D-DSA reconstruction and color flow analysis, are also covered. These new MRI and DSA techniques increase diagnostic accuracy, improve understanding of the pathophysiology and natural history of neurovascular disease, inform and guide treatment, and may provide risk stratification for patients being considered for therapy.

Design and validation of a modular micro-robotic system for the mechanical characterization of soft tissues.

The mechanical properties of tissues are critical design parameters for biomaterials and regenerative therapies seeking to restore functionality after disease or injury. Characterizing the mechanical properties of native tissues and extracellular matrix throughout embryonic development helps us understand the microenvironments that promote growth and remodeling, activities critical for biomaterials to support. The mechanical characterization of small, soft materials like the embryonic tissues of the mouse, an established mammalian model for development, is challenging due to difficulties in handling minute geometries and resolving forces of low magnitude. While uniaxial tensile testing is the physiologically relevant modality to characterize tissues that are loaded in tension in vivo, there are no commercially available instruments that can simultaneously measure sufficiently low tensile force magnitudes, directly measure sample deformation, keep samples hydrated throughout testing, and effectively grip minute geometries to test small tissues. To address this gap, we developed a micromanipulator and spring system that can mechanically characterize small, soft materials under tension. We demonstrate the capability of this system to measure the force contribution of soft materials, silicone, fibronectin sheets, and fibrin gels with a 5 nN - 50 µN force resolution and perform a variety of mechanical tests. Additionally, we investigated murine embryonic tendon mechanics, demonstrating the instrument can measure differences in mechanics of small, soft tissues as a function of developmental stage. This system can be further utilized to mechanically characterize soft biomaterials and small tissues and provide physiologically relevant parameters for designing scaffolds that seek to emulate native tissue mechanics. STATEMENT OF SIGNIFICANCE: The mechanical properties of cellular microenvironments are critical parameters that contribute to the modulation of tissue growth and remodeling. The field of tissue engineering endeavors to recapitulate these microenvironments in order to construct tissues de novo. Therefore, it is crucial to uncover the mechanical properties of the cellular microenvironment during tissue formation. Here, we present a system capable of acquiring microscale forces and optically measuring sample deformation to calculate the stress-strain response of soft, embryonic tissues under tension, and easily adaptable to accommodate biomaterials of various sizes and stiffnesses. Altogether, this modular system enables researchers to probe the unknown mechanical properties of soft tissues throughout development to inform the engineering of physiologically relevant microenvironments.

Divergence-Free Constrained Phase Unwrapping and Denoising for 4D Flow MRI Using Weighted Least-Squares.

A novel divergence-free constrained phase unwrapping method was proposed and evaluated for 4D flow MRI. The unwrapped phase field was obtained by integrating the phase variations estimated from the wrapped phase data using weighted least-squares. The divergence-free constraint for incompressible blood flow was incorporated to regulate and denoise the resulting phase field. The proposed method was tested on synthetic phase data of left ventricular flow and in vitro 4D flow measurement of Poiseuille flow. The method was additionally applied to in vivo 4D flow measurements in the thoracic aorta from 30 human subjects. The performance of the proposed method was compared to the state-of-the-art 4D single-step Laplacian algorithm. The synthetic phase data were completely unwrapped by the proposed method for all the cases with velocity encoding (venc) as low as 20% of the maximum velocity and signal-to-noise ratio as low as 5. The in vitro Poiseuille flow data were completely unwrapped with a 60% increase in the velocity-to-noise ratio. For the in-vivo aortic datasets with venc ratio less than 0.4, the proposed method significantly improved the success rate by as much as 40% and reduced the velocity error levels by a factor of 10 compared to the state-of-the-art method. The divergence-free constrained method exhibits reliability and robustness on phase unwrapping and shows improved accuracy of velocity and hemodynamic quantities by unwrapping the low-venc 4D flow MRI data.

Recent Advances in Biomechanical Characterization of Thoracic Aortic Aneurysms.

Thoracic aortic aneurysm (TAA) is a focal enlargement of the thoracic aorta, but the etiology of this disease is not fully understood. Previous work suggests that various genetic syndromes, congenital defects such as bicuspid aortic valve, hypertension, and age are associated with TAA formation. Though occurrence of TAAs is rare, they can be life-threatening when dissection or rupture occurs. Prevention of these adverse events often requires surgical intervention through full aortic root replacement or implantation of endovascular stent grafts. Currently, aneurysm diameters and expansion rates are used to determine if intervention is warranted. Unfortunately, this approach oversimplifies the complex aortopathy. Improving treatment of TAAs will likely require an increased understanding of the biological and biomechanical factors contributing to the disease. Past studies have substantially contributed to our knowledge of TAAs using various ex vivo, in vivo, and computational methods to biomechanically characterize the thoracic aorta. However, any singular approach typically focuses on only material properties of the aortic wall, intra-aneurysmal hemodynamics, or in vivo vessel dynamics, neglecting combinatorial factors that influence aneurysm development and progression. In this review, we briefly summarize the current understanding of TAA causes, treatment, and progression, before discussing recent advances in biomechanical studies of TAAs and possible future directions. We identify the need for comprehensive approaches that combine multiple characterization methods to study the mechanisms contributing to focal weakening and rupture. We hope this summary and analysis will inspire future studies leading to improved prediction of thoracic aneurysm progression and rupture, improving patient diagnoses and outcomes.

Computational modeling of drug transport and mixing in the chemofilter device: enhancing the removal of chemotherapeutics from circulation.

Intra-arterial chemotherapy (IAC) is the preferred treatment for non-resectable hepatocellular carcinoma. A large fraction of IAC drugs, e.g., Doxorubicin, pass into systemic circulation, causing cardiac toxicity and reducing effectiveness of the procedure. These excessive drugs can be captured by the Chemofilter-a 3D-printable, catheter-based device deployed in a vein downstream of the liver during IAC. In this study, alternative configurations of the Chemofilter device were compared by evaluating their hemodynamic and filtration performance through multiphysics computational fluid dynamics simulations. Two designs were evaluated, a honeycomb-like structure of parallel hexagonal channels (honeycomb Chemofilter) and a cubic lattice of struts (strutted Chemofilter). The computationally optimized Chemofilter design contains three honeycomb stages, each perforated and twisted, which improved Doxorubicin adsorption by 44.6% compared to a straight channel design. The multiphysics simulations predicted an overall 66.8% decrease in concentration with a 2.9 mm-Hg pressure drop across the optimized device compared to a 50% concentration decrease observed during in-vivo experiments conducted with the strutted Chemofilter. The Doxorubicin transport simulations demonstrated the effectiveness of the Chemofilter in removing excessive drugs from circulation while minimizing pressure drop and eliminating flow stagnation regions prone to thrombosis. These results demonstrate the value of the multiphysics modeling approach in device optimization and experimental burden reduction.