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We present a pipeline to quantify biomechanical environment of the brain using solely MRI-derived data in order to elucidate the role of biomechanical factors in neurodegenerative disorders. Neurological disorders, like Alzheimer's and Parkinson's diseases, are associated with physical changes, including the accumulation of amyloid-ß and tau proteins, damage to the cerebral vasculature, hypertension, atrophy of the cortical gray matter, and lesions of the periventricular white matter. Alterations in the external mechanical environment of cells can trigger pathological processes, and it is known that AD causes reduced stiffness in the brain tissue during degeneration. However, there appears to be a significant lag time between microscale changes and macroscale obstruction of neurological function in the brain. Here, we present a pipeline to quantify the whole brain biomechanical environment to bridge the gap in understanding how underlying brain changes affect macroscale brain biomechanics. This pipeline enables image-based quantification of subject-specific displacement field of the whole brain to subject-specific strain, strain rate, and stress across 133 labeled functional brain regions. We have focused our development efforts on utilizing solely MRI-derived data to facilitate clinical applicability of our approach and have emphasized automation in all aspects of our methods to reduce operator dependance. Our pipeline has the potential to improve early detection of neurological disorders and facilitate the identification of disease before widespread, irreversible damage has occurred.
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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.
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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.
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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.
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Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Hemodinámica , Algoritmos , Aorta Torácica/diagnóstico por imagen , Velocidad del Flujo SanguíneoRESUMEN
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.
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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.
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Aneurisma Roto , Aneurisma Intracraneal , Humanos , Hemodinámica , Arterias , Estrés MecánicoRESUMEN
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.
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Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Velocidad del Flujo Sanguíneo , Imagen por Resonancia Magnética/métodos , Aorta/diagnóstico por imagen , Estrés Mecánico , HemodinámicaRESUMEN
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.
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Imagenología Tridimensional , Imagen por Resonancia Magnética , Velocidad del Flujo Sanguíneo , Humanos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Flujo Pulsátil , Reproducibilidad de los ResultadosRESUMEN
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.
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Aneurisma Intracraneal , Imagen por Resonancia Magnética , Velocidad del Flujo Sanguíneo , Humanos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Relación Señal-RuidoRESUMEN
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.
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Aneurisma Intracraneal , Malformaciones Arteriovenosas Intracraneales , Humanos , Aneurisma Intracraneal/terapia , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Hemodinámica/fisiología , Imagen por Resonancia Magnética , Estrés MecánicoRESUMEN
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.
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Aneurisma Intracraneal , Imagen por Resonancia Magnética , Velocidad del Flujo Sanguíneo , Hemodinámica , Humanos , Imagenología Tridimensional , Aneurisma Intracraneal/diagnóstico por imagen , Estrés MecánicoRESUMEN
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.
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Procedimientos Quirúrgicos Robotizados , Animales , Materiales Biocompatibles , Matriz Extracelular , Fenómenos Mecánicos , Ratones , Estrés Mecánico , Ingeniería de TejidosRESUMEN
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.
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Imagenología Tridimensional , Variación de la Fase , Algoritmos , Velocidad del Flujo Sanguíneo , Humanos , Imagen por Resonancia Magnética , Fantasmas de Imagen , Reproducibilidad de los ResultadosRESUMEN
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.
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Aneurisma , Aneurisma Intracraneal , Angiografía de Substracción Digital , Medios de Contraste , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia MagnéticaRESUMEN
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.
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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.
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Hidrodinámica , Programas Informáticos , Simulación por Computador , Modelos CardiovascularesRESUMEN
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.
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Antineoplásicos/metabolismo , Simulación por Computador , Filtración/instrumentación , Transporte Biológico , Presión , TemperaturaRESUMEN
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.
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Fenómenos Biomecánicos , Diagnóstico por Imagen/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma/diagnóstico por imagen , Animales , Arterias/diagnóstico por imagen , Velocidad del Flujo Sanguíneo/fisiología , Simulación por Computador , Toma de Decisiones , Progresión de la Enfermedad , Hemodinámica , Humanos , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Aneurisma Intracraneal/terapia , Modelos Cardiovasculares , Periodo Posoperatorio , Riesgo , Tomografía Computarizada por Rayos X , Investigación Biomédica TraslacionalRESUMEN
This work introduces a 4D flow magnetic resonance imaging (MRI) pressure reconstruction method which employs weighted least-squares (WLS) for pressure integration. Pressure gradients are calculated from the velocity fields, and velocity errors are estimated from the velocity divergence for incompressible flow. Pressure gradient errors are estimated by propagating the velocity errors through Navier-Stokes momentum equation. A weight matrix is generated based on the pressure gradient errors, then employed for pressure reconstruction. The pressure reconstruction method was demonstrated and analyzed using synthetic velocity fields as well as Poiseuille flow measured using in vitro 4D flow MRI. Performance of the proposed WLS method was compared to the method of solving the pressure Poisson equation which has been the primary method used in the previous studies. Error analysis indicated that the proposed method is more robust to velocity measurement errors. Improvement on pressure results was found to be more significant for the cases with spatially-varying velocity error level, with reductions in error ranging from 50% to over 200%. Finally, the method was applied to flow in patient-specific cerebral aneurysms. Validation was performed with in vitro flow data collected using Particle Tracking Velocimetry (PTV) and in vivo flow measurement obtained using 4D flow MRI. Pressure calculated by WLS, as opposed to the Poisson equation, was more consistent with the flow structures and showed better agreement between the in vivo and in vitro data. These results suggest the utility of WLS method to obtain reliable pressure field from clinical flow measurement data.
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Algoritmos , Imagen por Resonancia Magnética , Velocidad del Flujo Sanguíneo , Humanos , Análisis de los Mínimos Cuadrados , Movimiento (Física) , Reproducibilidad de los ResultadosRESUMEN
Typical approaches to patient-specific haemodynamic studies of cerebral aneurysms use image-based computational fluid dynamics (CFD) and seek to statistically correlate parameters such as wall shear stress (WSS) and oscillatory shear index (OSI) to risk of growth and rupture. However, such studies have reported contradictory results, emphasizing the need for in-depth multi-modality haemodynamic metric evaluation. In this work, we used in vivo 4D flow MRI data to inform in vitro particle velocimetry and CFD modalities in two patient-specific cerebral aneurysm models (basilar tip and internal carotid artery). Pulsatile volumetric particle velocimetry experiments were conducted, and the particle images were processed using Shake-the-Box, a particle tracking method. Distributions of normalized WSS and relative residence time were shown to be highly yet inconsistently affected by minor flow field and spatial resolution variations across modalities, and specific relationships among these should be explored in future work. Conversely, OSI, a non-dimensional parameter, was shown to be more robust to the varying assumptions, limitations and spatial resolutions of each subject and modality. These results suggest a need for further multi-modality analysis as well as development of non-dimensional haemodynamic parameters and correlation of such metrics to aneurysm risk of growth and rupture.