Ruth Okamoto - Academia.edu (original) (raw)

Papers by Ruth Okamoto

ASME 2010 Summer Bioengineering Conference, Parts A and B, 2010

ABSTRACT The relationship between skull acceleration and brain injury is not well understood, in ... more ABSTRACT The relationship between skull acceleration and brain injury is not well understood, in large part because of the challenge of visualizing the brain’s mechanical response in vivo. This difficulty also complicates the validation of computational mechanics predictions.Our dynamic magnetic resonance (MR) imaging suggests an important role for the attachments between brain and skull. Here, we present an MRI-based method for identifying the dominant modes of brain displacement relative to the skull during angular acceleration of the head, and apply it to study brain/skull interactions in live volunteers. The approach was to estimate dynamic intracranial displacement fields from a sequence of tagged MR images of the brain and skull, then identify dominant displacement modes using principal component (PC) analysis. After verifying the method through analysis of a simulated 2-D vibrating plate and MR images of a cylindrical gel phantom, the method was applied to show that the dominant mode of brain/skull interaction is one of sliding arrested by brain/skull meninges in a few specific regions.

ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011

ABSTRACT The forces exerted on the flagellum of the swimming alga Chlamydomonas reinhardtii by su... more ABSTRACT The forces exerted on the flagellum of the swimming alga Chlamydomonas reinhardtii by surrounding fluid are estimated from video data. “Wild-type” cells, as well as cells lacking inner dynein arms (ida3) and cells lacking outer dynein arms (oda2) were imaged (350 fps; 125 nm). Digital image registration and sorting algorithms provide high-resolution descriptions of the kinematics of the cell body and flagellum. The swimming cell is then modeled as an ellipsoid in Stokes flow, propelled by viscous forces that depend linearly on the velocity of the flagellum. The coefficients (CN and CT) that related normal and tangent forces on the flagellum to corresponding velocity components are estimated from equilibrium requirements. Their values are consistent among all three genotypes and similar to theoretical predictions.

ASME 2007 Summer Bioengineering Conference, 2007

ABSTRACT Remodeling of arteries in response to altered loads is an area of intense interest to ca... more ABSTRACT Remodeling of arteries in response to altered loads is an area of intense interest to cardio-vascular clinicians and researchers. In humans, changes due to cardiovascular diseases (e.g. aortic dilatation) may occur slowly over many years, and mathematical models that describe the remodeling response are needed for predicting the course, and possible treatment, of these diseases. Recently, Humphrey and co-workers have proposed constrained mixture models [1] that consider local stresses in the arterial wall to be the sum of contributions from collagen, elastic fibers, and vascular smooth muscle cells (VSMCs). While numerous studies (e.g., [2]) have considered the active response of VSMCs in large arteries under quasi-static conditions, little is known about the mechanical response of VSMCs to continuous cyclic stretch. We have chosen 3-D bio-artificial tissue constructs as a model system in which to study the response of VSMCs to continuous cyclic stretch. However, VSMCs undergo a shift from a contractile phenotype to a de-differentiated phenotype during culture [3]. Some investigators have suggested that serum deprivation can induce re-differentiation toward a more contractile phenotype [4, 5]. The goal of our study was to compare the effect of incubation conditions on the active responses of VSMCs in 3-D tissue constructs to continuous cyclic stretch.

Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1999

Patients with a dilated ascending aorta are at risk for life-threatening aortic dissection or rup... more Patients with a dilated ascending aorta are at risk for life-threatening aortic dissection or rupture. It is assumed that both abnormal mechanical properties and increased stresses contribute to this risk, but the relative weights of these factors are not well understood. To assess the mechanical properties of dilated ascending aorta, we obtained specimens removed during elective surgery. We used biaxial

ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Associat... more ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

Plant Physiology, 2015

The cell wall consists of cellulose microfibrils embedded within a matrix of hemicellulose and pe... more The cell wall consists of cellulose microfibrils embedded within a matrix of hemicellulose and pectin. Cellulose microfibrils are synthesized at the plasma membrane, whereas matrix polysaccharides are synthesized in the Golgi apparatus and secreted. The trafficking of vesicles containing cell wall components is thought to depend on actin-myosin. Here, we implicate microtubules in this process through studies of the kinesin-4 family member, Fragile Fiber1 (FRA1). In an fra1-5 knockout mutant, the expansion rate of the inflorescence stem is halved compared with the wild type along with the thickness of both primary and secondary cell walls. Nevertheless, cell walls in fra1-5 have an essentially unaltered composition and ultrastructure. A functional triple green fluorescent protein-tagged FRA1 fusion protein moves processively along cortical microtubules, and its abundance and motile density correlate with growth rate. Motility of FRA1 and cellulose synthase complexes is independent, indicating that FRA1 is not directly involved in cellulose biosynthesis; however, the secretion rate of fucose-alkyne-labeled pectin is greatly decreased in fra1-5, and the mutant has Golgi bodies with fewer cisternae and enlarged vesicles. Based on our results, we propose that FRA1 contributes to cell wall production by transporting Golgi-derived vesicles along cortical microtubules for secretion.

Medical Imaging 2014: Biomedical Applications in Molecular, Structural, and Functional Imaging, 2014

In magnetic resonance elastography (MRE), displacement fields from shear waves are inverted to es... more In magnetic resonance elastography (MRE), displacement fields from shear waves are inverted to estimate underlying material properties. Modulus differences detected by MRE may be used to distinguish tumors or other localized pathology in tissue. The accuracy of modulus estimates depends on the choice of the assumed constitutive model, as well as on the inversion algorithm, image resolution, and signal-to-noise ratio. In particular, in simpler inversion methods such as direct inversion and three-dimensional local frequency estimation (3D-LFE) the constitutive model is minimal (linear, elastic or viscoelastic, and isotropic) and the simplifying assumption of local homogeneity is usually made. The assumption of local homogeneity is often inaccurate [1], since the shear wavelength is typically comparable to the size of the structures of interest. Notably, the residual error (in direct inversion) between the model and the experimental data increases sharply at the boundaries of inclusions, while the "certainty" of the 3D-LFE estimate decreases. These error metrics may be used to detect local stiffness heterogeneity, as well as indicate variations in appropriate constitutive models. The utility of model uncertainty is demonstrated in simulations and with MRE data from a heterogeneous gel phantom.

Volume 2: Biomedical and Biotechnology, 2012

ABSTRACT Axonal fiber tracts in white matter of the brain form anisotropic structures. It is assu... more ABSTRACT Axonal fiber tracts in white matter of the brain form anisotropic structures. It is assumed that this structural anisotropy causes mechanical anisotropy, making white matter tissue stiffer along the axonal fiber direction. This, in turn, will affect the mechanical loading of axonal tracts during traumatic brain injury (TBI). The goal of this study is to use a combination of in-vitro tests to characterize the mechanical anisotropy of white matter and compare it to gray matter, which is thought to be structurally and mechanically isotropic. A more complete understanding of the mechanical anisotropy of brain tissue will provide more accurate information for computational simulations of brain injury.

Handbook of Imaging in Biological Mechanics, 2014

The purpose of this study was to obtain normative data using magnetic resonance elastography (MRE... more The purpose of this study was to obtain normative data using magnetic resonance elastography (MRE) to: [a] obtain estimates of the shear modulus of human cerebral tissue in vivo, and [b] assess a possible age dependence of the shear modulus of cerebral tissue in healthy adult volunteers. MR elastography studies were performed on tissue-simulating gelatin phantoms and 25 healthy adult volunteers. The data were analyzed using spatio-temporal filters and a local frequency estimating algorithm. Statistical analysis was performed using a paired t-test. The mean shear stiffness of cerebral white matter was 13.6 kPa (95% CI 12.3 to 14.8 kPa); while that of gray matter was lower at 5.22 kPa (95% CI 4.76 to 5.66 kPa). The difference was statistically significant (p < 0.0001).

Volume 2: Biomedical and Biotechnology, 2012

ABSTRACT Mathematical modeling and computer simulations are widely used for understanding traumat... more ABSTRACT Mathematical modeling and computer simulations are widely used for understanding traumatic brain injury (TBI). However, accurate tissue parameters are needed, especially for the brain in vivo. In this study, we used the ferret as the animal model because it is the smallest mammal with a folded brain and significant white matter tracts. Magnetic resonance elastography (MRE) has proven useful for in vivo measurement of biological tissue properties. Mechanical properties of the ferret brain over a range of frequencies from 400–800 Hz were studied using MRE. Experiment results show both that storage and loss modulus increases with frequency and that dissipative effects in the white matter (characterized by the loss modulus G″) were significant larger than in gray matter.

ASME 2012 Summer Bioengineering Conference, Parts A and B, 2012

ABSTRACT Cilia are thin subcellular organelles that bend actively to propel fluid. The ciliary cy... more ABSTRACT Cilia are thin subcellular organelles that bend actively to propel fluid. The ciliary cytoskeleton (the axoneme) consists of nine outer microtubule doublets surrounding a central pair of singlet microtubules. Large bending deformations of the axoneme involve relative sliding of the outer doublets, driven by the motor protein dynein. Ciliary structure and function have been studied extensively, but details of the mechanics and coordination of the axoneme remain unclear. In particular, dynein activity must be switched on and off at specific times and locations to produce an oscillatory, propulsive beat. Leading hypotheses assert that mechanical feedback plays a role in the control of dynein activity, but these ideas remain speculative.

American Journal of Gastroenterology - AMER J GASTROENTEROL, 2000

ABSTRACT

PLoS ONE, 2011

Non-destructive measurement of acceleration-induced displacement fields within a closed object is... more Non-destructive measurement of acceleration-induced displacement fields within a closed object is a fundamental challenge. Inferences of how the brain deforms following skull impact have thus relied largely on indirect estimates and course-resolution cadaver studies. We developed a magnetic resonance technique to quantitatively identify the modes of displacement of an accelerating soft object relative to an object enclosing it, and applied it to study acceleration-induced brain deformation in human volunteers. We show that, contrary to the prevailing hypotheses of the field, the dominant mode of interaction between the brain and skull in mild head acceleration is one of sliding arrested by meninges.

Physics in Medicine and Biology, 2011

Magnetic resonance elastography (MRE) is used to quantify the viscoelastic shear modulus, G

Physical Biology, 2013

In humans and many other mammals, the cortex (the outer layer of the brain) folds during developm... more In humans and many other mammals, the cortex (the outer layer of the brain) folds during development. The mechanics of folding are not well understood; leading explanations are either incomplete or at odds with physical measurements. We propose a mathematical model in which (i) folding is driven by tangential expansion of the cortex and (ii) deeper layers grow in response to the resulting stress. In this model the wavelength of cortical folds depends predictably on the rate of cortical growth relative to the rate of stress-induced growth. We show analytically and in simulations that faster cortical expansion leads to shorter gyral wavelengths; slower cortical expansion leads to long wavelengths or even smooth (lissencephalic) surfaces. No inner or outer (skull) constraint is needed to produce folding, but initial shape and mechanical heterogeneity influence the final shape. The proposed model predicts patterns of stress in the tissue that are consistent with experimental observations.

Magnetic Resonance Imaging, 2009

The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomecha... more The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomechanical imaging technique to address biomechanical pathways of atherosclerotic progression and regression in vivo using a 3D fluid-structure interaction (FSI) model. Initial in vivo study was carried out in an early plaque model in pigs that underwent balloon-overstretch injury to the left carotid arteries. Consecutive MRI scans were performed while the pigs were maintained on high cholesterol (progression) or normal chow (regression), with an injection of a plaque-targeted contrast agent, Gadofluorine M. At the end of study, the specimens of carotid arterial segments were dissected and underwent dedicated mechanical testing to determine their material properties. 3D FSI computational model was applied to calculate structure stress and strain distribution. The plaque structure resembles early plaque with thickened intima. Lower maximal flow shear stress correlates with the growth of plaque volume during progression, but not during regression. In contrast, maximal principle structure stress/stain (stress-P1 and strain-P1) were shown to correlate strongly with the change in the plaque dimension during regression, but moderately during progression. This MRI-based biomechanical imaging method may allow for noninvasive dynamic assessment of local hemodynamic forces on the development of atherosclerotic plaques in vivo.

The Journal of Thoracic and Cardiovascular Surgery, 2003

The influence of mechanical properties on wall stress and distensibility of the Objectives: We so... more The influence of mechanical properties on wall stress and distensibility of the Objectives: We sought to determine how intrinsic mechanical properties of dilated ascending aorta influence in vivo distensibility and wall stress, potential contributing factors to the risk of aortic rupture and dissection.

Journal of The Royal Society Interface, 2010

This study describes the measurement of fields of relative displacement between the brain and the... more This study describes the measurement of fields of relative displacement between the brain and the skull in vivo by tagged magnetic resonance imaging and digital image analysis. Motion of the brain relative to the skull occurs during normal activity, but if the head undergoes high accelerations, the resulting large and rapid deformation of neuronal and axonal tissue can lead to long-term disability or death. Mathematical modelling and computer simulation of acceleration-induced traumatic brain injury promise to illuminate the mechanisms of axonal and neuronal pathology, but numerical studies require knowledge of boundary conditions at the brain -skull interface, material properties and experimental data for validation. The current study provides a dense set of displacement measurements in the human brain during mild frontal skull impact constrained to the sagittal plane. Although head motion is dominated by translation, these data show that the brain rotates relative to the skull. For these mild events, characterized by linear decelerations near 1.5g (g ¼ 9.81 m s 22 ) and angular accelerations of 120 -140 rad s 22 , relative brain -skull displacements of 2-3 mm are typical; regions of smaller displacements reflect the tethering effects of brain -skull connections. Strain fields exhibit significant areas with maximal principal strains of 5 per cent or greater. These displacement and strain fields illuminate the skull -brain boundary conditions, and can be used to validate simulations of brain biomechanics. Relative brain motion during mild impact Y. Feng et al. 1685

Journal of Cardiovascular Magnetic Resonance, 2008

Fluid shear stress was thought to lead to atherosclerotic plaque progression, but such measuremen... more Fluid shear stress was thought to lead to atherosclerotic plaque progression, but such measurement procedures are often invasive. The goal of the present study is to address the biomechanical pathways of atherosclerosis progression and regression with our non-invasive MRI methods and a 3D fluid-structure interaction (FSI) model. The study was performed in a large animal atherosclerotic model.

Journal of Biomechanics, 2013

Characterization of the dynamic mechanical behavior of brain tissue is essential for understandin... more Characterization of the dynamic mechanical behavior of brain tissue is essential for understanding and simulating the mechanisms of traumatic brain injury (TBI). Changes in mechanical properties may also reflect changes in the brain due to aging or disease. In this study, we used magnetic resonance elastography (MRE) to measure the viscoelastic properties of ferret brain tissue in vivo. Threedimensional (3D) displacement fields were acquired during wave propagation in the brain induced by harmonic excitation of the skull at 400 Hz, 600 Hz and 800 Hz. Shear waves with wavelengths in the order of millimeters were clearly visible in the displacement field, in strain fields, and in the curl of displacement field (which contains no contributions from longitudinal waves). Viscoelastic parameters (storage and loss moduli) governing dynamic shear deformation were estimated in gray and white matter for these excitation frequencies. To characterize the reproducibility of measurements, two ferrets were studied on three different dates each. Estimated viscoelastic properties of white matter in the ferret brain were generally similar to those of gray matter and consistent between animals and scan dates. In both tissue types G 0 increased from approximately 3 kPa at 400 Hz to 7 kPa at 800 Hz and G 00 increased from approximately 1 kPa at 400 Hz to 2 kPa at 800 Hz. These measurements of shear wave propagation in the ferret brain can be used to both parameterize and validate finite element models of brain biomechanics. assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity. Physics in Medicine and Biology 52, 7281-7294. Kleiven, S., 2002. Finite element modeling of the human head. Ph.D. Dissertation. A new method to measure cortical growth in the developing brain.

ASME 2010 Summer Bioengineering Conference, Parts A and B, 2010

ABSTRACT The relationship between skull acceleration and brain injury is not well understood, in ... more ABSTRACT The relationship between skull acceleration and brain injury is not well understood, in large part because of the challenge of visualizing the brain’s mechanical response in vivo. This difficulty also complicates the validation of computational mechanics predictions.Our dynamic magnetic resonance (MR) imaging suggests an important role for the attachments between brain and skull. Here, we present an MRI-based method for identifying the dominant modes of brain displacement relative to the skull during angular acceleration of the head, and apply it to study brain/skull interactions in live volunteers. The approach was to estimate dynamic intracranial displacement fields from a sequence of tagged MR images of the brain and skull, then identify dominant displacement modes using principal component (PC) analysis. After verifying the method through analysis of a simulated 2-D vibrating plate and MR images of a cylindrical gel phantom, the method was applied to show that the dominant mode of brain/skull interaction is one of sliding arrested by brain/skull meninges in a few specific regions.

ASME 2011 Summer Bioengineering Conference, Parts A and B, 2011

ABSTRACT The forces exerted on the flagellum of the swimming alga Chlamydomonas reinhardtii by su... more ABSTRACT The forces exerted on the flagellum of the swimming alga Chlamydomonas reinhardtii by surrounding fluid are estimated from video data. “Wild-type” cells, as well as cells lacking inner dynein arms (ida3) and cells lacking outer dynein arms (oda2) were imaged (350 fps; 125 nm). Digital image registration and sorting algorithms provide high-resolution descriptions of the kinematics of the cell body and flagellum. The swimming cell is then modeled as an ellipsoid in Stokes flow, propelled by viscous forces that depend linearly on the velocity of the flagellum. The coefficients (CN and CT) that related normal and tangent forces on the flagellum to corresponding velocity components are estimated from equilibrium requirements. Their values are consistent among all three genotypes and similar to theoretical predictions.

ASME 2007 Summer Bioengineering Conference, 2007

ABSTRACT Remodeling of arteries in response to altered loads is an area of intense interest to ca... more ABSTRACT Remodeling of arteries in response to altered loads is an area of intense interest to cardio-vascular clinicians and researchers. In humans, changes due to cardiovascular diseases (e.g. aortic dilatation) may occur slowly over many years, and mathematical models that describe the remodeling response are needed for predicting the course, and possible treatment, of these diseases. Recently, Humphrey and co-workers have proposed constrained mixture models [1] that consider local stresses in the arterial wall to be the sum of contributions from collagen, elastic fibers, and vascular smooth muscle cells (VSMCs). While numerous studies (e.g., [2]) have considered the active response of VSMCs in large arteries under quasi-static conditions, little is known about the mechanical response of VSMCs to continuous cyclic stretch. We have chosen 3-D bio-artificial tissue constructs as a model system in which to study the response of VSMCs to continuous cyclic stretch. However, VSMCs undergo a shift from a contractile phenotype to a de-differentiated phenotype during culture [3]. Some investigators have suggested that serum deprivation can induce re-differentiation toward a more contractile phenotype [4, 5]. The goal of our study was to compare the effect of incubation conditions on the active responses of VSMCs in 3-D tissue constructs to continuous cyclic stretch.

Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 1999

Patients with a dilated ascending aorta are at risk for life-threatening aortic dissection or rup... more Patients with a dilated ascending aorta are at risk for life-threatening aortic dissection or rupture. It is assumed that both abnormal mechanical properties and increased stresses contribute to this risk, but the relative weights of these factors are not well understood. To assess the mechanical properties of dilated ascending aorta, we obtained specimens removed during elective surgery. We used biaxial

ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Associat... more ABSTRACT Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

Plant Physiology, 2015

The cell wall consists of cellulose microfibrils embedded within a matrix of hemicellulose and pe... more The cell wall consists of cellulose microfibrils embedded within a matrix of hemicellulose and pectin. Cellulose microfibrils are synthesized at the plasma membrane, whereas matrix polysaccharides are synthesized in the Golgi apparatus and secreted. The trafficking of vesicles containing cell wall components is thought to depend on actin-myosin. Here, we implicate microtubules in this process through studies of the kinesin-4 family member, Fragile Fiber1 (FRA1). In an fra1-5 knockout mutant, the expansion rate of the inflorescence stem is halved compared with the wild type along with the thickness of both primary and secondary cell walls. Nevertheless, cell walls in fra1-5 have an essentially unaltered composition and ultrastructure. A functional triple green fluorescent protein-tagged FRA1 fusion protein moves processively along cortical microtubules, and its abundance and motile density correlate with growth rate. Motility of FRA1 and cellulose synthase complexes is independent, indicating that FRA1 is not directly involved in cellulose biosynthesis; however, the secretion rate of fucose-alkyne-labeled pectin is greatly decreased in fra1-5, and the mutant has Golgi bodies with fewer cisternae and enlarged vesicles. Based on our results, we propose that FRA1 contributes to cell wall production by transporting Golgi-derived vesicles along cortical microtubules for secretion.

Medical Imaging 2014: Biomedical Applications in Molecular, Structural, and Functional Imaging, 2014

In magnetic resonance elastography (MRE), displacement fields from shear waves are inverted to es... more In magnetic resonance elastography (MRE), displacement fields from shear waves are inverted to estimate underlying material properties. Modulus differences detected by MRE may be used to distinguish tumors or other localized pathology in tissue. The accuracy of modulus estimates depends on the choice of the assumed constitutive model, as well as on the inversion algorithm, image resolution, and signal-to-noise ratio. In particular, in simpler inversion methods such as direct inversion and three-dimensional local frequency estimation (3D-LFE) the constitutive model is minimal (linear, elastic or viscoelastic, and isotropic) and the simplifying assumption of local homogeneity is usually made. The assumption of local homogeneity is often inaccurate [1], since the shear wavelength is typically comparable to the size of the structures of interest. Notably, the residual error (in direct inversion) between the model and the experimental data increases sharply at the boundaries of inclusions, while the "certainty" of the 3D-LFE estimate decreases. These error metrics may be used to detect local stiffness heterogeneity, as well as indicate variations in appropriate constitutive models. The utility of model uncertainty is demonstrated in simulations and with MRE data from a heterogeneous gel phantom.

Volume 2: Biomedical and Biotechnology, 2012

ABSTRACT Axonal fiber tracts in white matter of the brain form anisotropic structures. It is assu... more ABSTRACT Axonal fiber tracts in white matter of the brain form anisotropic structures. It is assumed that this structural anisotropy causes mechanical anisotropy, making white matter tissue stiffer along the axonal fiber direction. This, in turn, will affect the mechanical loading of axonal tracts during traumatic brain injury (TBI). The goal of this study is to use a combination of in-vitro tests to characterize the mechanical anisotropy of white matter and compare it to gray matter, which is thought to be structurally and mechanically isotropic. A more complete understanding of the mechanical anisotropy of brain tissue will provide more accurate information for computational simulations of brain injury.

Handbook of Imaging in Biological Mechanics, 2014

The purpose of this study was to obtain normative data using magnetic resonance elastography (MRE... more The purpose of this study was to obtain normative data using magnetic resonance elastography (MRE) to: [a] obtain estimates of the shear modulus of human cerebral tissue in vivo, and [b] assess a possible age dependence of the shear modulus of cerebral tissue in healthy adult volunteers. MR elastography studies were performed on tissue-simulating gelatin phantoms and 25 healthy adult volunteers. The data were analyzed using spatio-temporal filters and a local frequency estimating algorithm. Statistical analysis was performed using a paired t-test. The mean shear stiffness of cerebral white matter was 13.6 kPa (95% CI 12.3 to 14.8 kPa); while that of gray matter was lower at 5.22 kPa (95% CI 4.76 to 5.66 kPa). The difference was statistically significant (p < 0.0001).

Volume 2: Biomedical and Biotechnology, 2012

ABSTRACT Mathematical modeling and computer simulations are widely used for understanding traumat... more ABSTRACT Mathematical modeling and computer simulations are widely used for understanding traumatic brain injury (TBI). However, accurate tissue parameters are needed, especially for the brain in vivo. In this study, we used the ferret as the animal model because it is the smallest mammal with a folded brain and significant white matter tracts. Magnetic resonance elastography (MRE) has proven useful for in vivo measurement of biological tissue properties. Mechanical properties of the ferret brain over a range of frequencies from 400–800 Hz were studied using MRE. Experiment results show both that storage and loss modulus increases with frequency and that dissipative effects in the white matter (characterized by the loss modulus G″) were significant larger than in gray matter.

ASME 2012 Summer Bioengineering Conference, Parts A and B, 2012

ABSTRACT Cilia are thin subcellular organelles that bend actively to propel fluid. The ciliary cy... more ABSTRACT Cilia are thin subcellular organelles that bend actively to propel fluid. The ciliary cytoskeleton (the axoneme) consists of nine outer microtubule doublets surrounding a central pair of singlet microtubules. Large bending deformations of the axoneme involve relative sliding of the outer doublets, driven by the motor protein dynein. Ciliary structure and function have been studied extensively, but details of the mechanics and coordination of the axoneme remain unclear. In particular, dynein activity must be switched on and off at specific times and locations to produce an oscillatory, propulsive beat. Leading hypotheses assert that mechanical feedback plays a role in the control of dynein activity, but these ideas remain speculative.

American Journal of Gastroenterology - AMER J GASTROENTEROL, 2000

ABSTRACT

PLoS ONE, 2011

Non-destructive measurement of acceleration-induced displacement fields within a closed object is... more Non-destructive measurement of acceleration-induced displacement fields within a closed object is a fundamental challenge. Inferences of how the brain deforms following skull impact have thus relied largely on indirect estimates and course-resolution cadaver studies. We developed a magnetic resonance technique to quantitatively identify the modes of displacement of an accelerating soft object relative to an object enclosing it, and applied it to study acceleration-induced brain deformation in human volunteers. We show that, contrary to the prevailing hypotheses of the field, the dominant mode of interaction between the brain and skull in mild head acceleration is one of sliding arrested by meninges.

Physics in Medicine and Biology, 2011

Magnetic resonance elastography (MRE) is used to quantify the viscoelastic shear modulus, G

Physical Biology, 2013

In humans and many other mammals, the cortex (the outer layer of the brain) folds during developm... more In humans and many other mammals, the cortex (the outer layer of the brain) folds during development. The mechanics of folding are not well understood; leading explanations are either incomplete or at odds with physical measurements. We propose a mathematical model in which (i) folding is driven by tangential expansion of the cortex and (ii) deeper layers grow in response to the resulting stress. In this model the wavelength of cortical folds depends predictably on the rate of cortical growth relative to the rate of stress-induced growth. We show analytically and in simulations that faster cortical expansion leads to shorter gyral wavelengths; slower cortical expansion leads to long wavelengths or even smooth (lissencephalic) surfaces. No inner or outer (skull) constraint is needed to produce folding, but initial shape and mechanical heterogeneity influence the final shape. The proposed model predicts patterns of stress in the tissue that are consistent with experimental observations.

Magnetic Resonance Imaging, 2009

The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomecha... more The goal of the study is to develop a noninvasive magnetic resonance imaging (MRI)-based biomechanical imaging technique to address biomechanical pathways of atherosclerotic progression and regression in vivo using a 3D fluid-structure interaction (FSI) model. Initial in vivo study was carried out in an early plaque model in pigs that underwent balloon-overstretch injury to the left carotid arteries. Consecutive MRI scans were performed while the pigs were maintained on high cholesterol (progression) or normal chow (regression), with an injection of a plaque-targeted contrast agent, Gadofluorine M. At the end of study, the specimens of carotid arterial segments were dissected and underwent dedicated mechanical testing to determine their material properties. 3D FSI computational model was applied to calculate structure stress and strain distribution. The plaque structure resembles early plaque with thickened intima. Lower maximal flow shear stress correlates with the growth of plaque volume during progression, but not during regression. In contrast, maximal principle structure stress/stain (stress-P1 and strain-P1) were shown to correlate strongly with the change in the plaque dimension during regression, but moderately during progression. This MRI-based biomechanical imaging method may allow for noninvasive dynamic assessment of local hemodynamic forces on the development of atherosclerotic plaques in vivo.

The Journal of Thoracic and Cardiovascular Surgery, 2003

The influence of mechanical properties on wall stress and distensibility of the Objectives: We so... more The influence of mechanical properties on wall stress and distensibility of the Objectives: We sought to determine how intrinsic mechanical properties of dilated ascending aorta influence in vivo distensibility and wall stress, potential contributing factors to the risk of aortic rupture and dissection.

Journal of The Royal Society Interface, 2010

This study describes the measurement of fields of relative displacement between the brain and the... more This study describes the measurement of fields of relative displacement between the brain and the skull in vivo by tagged magnetic resonance imaging and digital image analysis. Motion of the brain relative to the skull occurs during normal activity, but if the head undergoes high accelerations, the resulting large and rapid deformation of neuronal and axonal tissue can lead to long-term disability or death. Mathematical modelling and computer simulation of acceleration-induced traumatic brain injury promise to illuminate the mechanisms of axonal and neuronal pathology, but numerical studies require knowledge of boundary conditions at the brain -skull interface, material properties and experimental data for validation. The current study provides a dense set of displacement measurements in the human brain during mild frontal skull impact constrained to the sagittal plane. Although head motion is dominated by translation, these data show that the brain rotates relative to the skull. For these mild events, characterized by linear decelerations near 1.5g (g ¼ 9.81 m s 22 ) and angular accelerations of 120 -140 rad s 22 , relative brain -skull displacements of 2-3 mm are typical; regions of smaller displacements reflect the tethering effects of brain -skull connections. Strain fields exhibit significant areas with maximal principal strains of 5 per cent or greater. These displacement and strain fields illuminate the skull -brain boundary conditions, and can be used to validate simulations of brain biomechanics. Relative brain motion during mild impact Y. Feng et al. 1685

Journal of Cardiovascular Magnetic Resonance, 2008

Fluid shear stress was thought to lead to atherosclerotic plaque progression, but such measuremen... more Fluid shear stress was thought to lead to atherosclerotic plaque progression, but such measurement procedures are often invasive. The goal of the present study is to address the biomechanical pathways of atherosclerosis progression and regression with our non-invasive MRI methods and a 3D fluid-structure interaction (FSI) model. The study was performed in a large animal atherosclerotic model.

Journal of Biomechanics, 2013

Characterization of the dynamic mechanical behavior of brain tissue is essential for understandin... more Characterization of the dynamic mechanical behavior of brain tissue is essential for understanding and simulating the mechanisms of traumatic brain injury (TBI). Changes in mechanical properties may also reflect changes in the brain due to aging or disease. In this study, we used magnetic resonance elastography (MRE) to measure the viscoelastic properties of ferret brain tissue in vivo. Threedimensional (3D) displacement fields were acquired during wave propagation in the brain induced by harmonic excitation of the skull at 400 Hz, 600 Hz and 800 Hz. Shear waves with wavelengths in the order of millimeters were clearly visible in the displacement field, in strain fields, and in the curl of displacement field (which contains no contributions from longitudinal waves). Viscoelastic parameters (storage and loss moduli) governing dynamic shear deformation were estimated in gray and white matter for these excitation frequencies. To characterize the reproducibility of measurements, two ferrets were studied on three different dates each. Estimated viscoelastic properties of white matter in the ferret brain were generally similar to those of gray matter and consistent between animals and scan dates. In both tissue types G 0 increased from approximately 3 kPa at 400 Hz to 7 kPa at 800 Hz and G 00 increased from approximately 1 kPa at 400 Hz to 2 kPa at 800 Hz. These measurements of shear wave propagation in the ferret brain can be used to both parameterize and validate finite element models of brain biomechanics. assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity. Physics in Medicine and Biology 52, 7281-7294. Kleiven, S., 2002. Finite element modeling of the human head. Ph.D. Dissertation. A new method to measure cortical growth in the developing brain.