Projects

Biomechanical Mechanisms in Arteriovenous Graft Failure

Francis Loth, Ph.D
Hisham S. Bassiouny, M.D
Paul F. Fischer, Ph.D
Thomas J. Royston, Ph.D
Sang-Wook Lee, M.S
David Smith, B.S

The objective of the research is to determine the role of fluid and solid stresses in the failure of arteriovenous (AV) dialysis grafts. The insights gained in this study will lead to significant improvements in the durability of AV grafts that are commonly used as a vascular access site for hemodialysis patients. Increased durability would reduce patient morbidity, pain and discomfort as well as reduce the cost of AV graft surgical procedures, currently one billion dollars per year in the United States alone. AV grafts often fail due to a flow limiting stenosis at the venous anastomosis caused by venous anastomotic intimal hyperplasia (VAIH). The AV circuit represents a unique hemodynamic environment in which transition to turbulence often occurs. High flow velocity and pressure fluctuations at the venous anastomosis induce vein-wall vibration. The level of vein-wall vibration has been correlated with VAIH in an animal model by previous researchers. However, the molecular and cellular cascade of events underlying VAIH and the importance of tensile stress and wall shear stress have not yet been examined. Our preliminary work shows that activity of mitogen-activated protein kinases (MAPKs) is increased in areas of elevated vein-wall vibration. MAPKs have been shown to be part of the complex cascade of intracellular signaling events that respond to shear stress stimulation in vascular smooth muscle cells (VSMC). This research is based on the hypothesis that biomechanical stimuli modulate VSMC proliferation and VAIH.

Specific Aims:
1) Measure in vivo the spatial distribution of vein-wall vibration in an AV graft end-to-side venous anastomosis canine model. Using a laser Doppler vibrometer, we are able to measure surface vibration without contacting the vein wall. These measurements are novel as, to the best of our knowledge, no direct measurements of vein-wall vibration in vivo have been published.

2) Determine the spatial distribution of fluid wall shear stress, pressure, and wall tensile stress at the anastomosis using computational method and in vitro experiments. Wall shear stresses will be computed numerically using a spectral element code, and laser Doppler anemometry measurements will be used for validation. Wall tensile stresses will be computed by a commercial finite element package.

3) Measure the spatial distribution of VAIH and elevated activity levels of MAPKs at the venous anastomosis using Western blotting and immunohistochemistry.

4) Identify the relationship between the above biomechanical variables, molecular events, and VAIH in order to elucidate the mechanisms involved in the development of VAIH in AV grafts.

An understanding of the biomechanical forces involved in triggering the molecular and cellular cascade of events underlying AV graft failure will help in the design of selective inhibitor drugs of biomechanically induced VAIH. The results of the research project will also lead to new grafting techniques for optimal fluid shear environment, minimization of tensile stress concentrations, and/or vibration reduction. In addition, this work may help in the design of inexpensive, vibration-based non-invasive instrumentation for diagnosis and monitoring of AV graft patency.

A Multimode Sonic and Ultrasonic Diagnostic Imaging Method
Development of a Novel Device that Integrates Existing Ultrasound Technology With New Acoustic Sensor Array

Thomas J. Royston, PhD, UIC
Francis Loth, PhD, UIC
Hisham Bassiouny, MD, University of Chicago
Todd Spohnholtz, M.S., UIC 
Bryn Martin, B.S., UIC

The goal of this project is to improve existing ultrasound (US) medical imaging technology by integrating a noninvasive acoustic sensor array that is capable of measuring biological sounds originating from within the human body. This Multimode sonic / US imaging technique will advance diagnostic capabilities beyond the state-of-the-art and will be ideal for retrofit on existing systems.

Measurement of naturally-occurring biological acoustic phenomena can augment conventional imaging technology by providing unique information about body material structure and system function. Sonic phenomena of diagnostic value can be derived from a wide range of biological functions, such as breath sounds, bowel sounds and vascular bruits. The acoustic sensor array aims to aid in diagnosis of pathological conditions through the detection of these and other sounds. The potential range of applications can be further expanded by coupling the multimode technology with vibroacoustography, where one noninvasively insonifies a localized region of tissue via focused modulated US.

The initial focus of this project will be to provide an improved diagnostic tool for common peripheral vascular complications associated with artiovenous (AV) grafts. The specific aim of this project is to develop and evaluate the capability of the proposed sonic / US diagnostic technology to track and predict AV graft failure.

Major tasks include:
1) Construction of the multimode system by combining a commercial US system with a novel sonic sensor array and associate instrumentation.

2) Calibration and improvement of its capability by conducting controlled phantom studies using simple and anatomically accurate geometries based on 3 dimensional in vivo US images.

3) Conducting of serial feasibility studies on 3 human AV graft patients.

The proposed Multimode sonic / US imaging device will be tested by applying an audible frequency (sonic) sensor array pad on the skin (or phantom) over which the peripheral vascular US probe is maneuvered. The US probe images the discrete sensors in the array in addition to the underlying anatomical structure. The array sensors detect and focus on diagnostically indicative surrounding biological tissues. The sonic array provides unique diagnostic information unobtainable via US capability and consequently, diagnostic value, of the sonic array.

Carotid Hemodynamics
Blood Flow Modeling inside a Human Carotid Artery: Experimental and Computational Studies

Francis Loth, Ph.D.
Paul Fischer, Ph.D.
Hisham Bassiouny, M.D.
Thomas Royston, Ph.D.
Olrick Bick, M.D.
Nicole Piersol, B.S.
Wojtek Kalata, B.S.
Seung Lee
Ramana Yedavalli, B.S.

The objective of this project is the development of a computational model that predicts the hemodynamics (forces resulting from blood flow) in subject-specific vascular geometries extracted from medical images. The long-term outcome would be the development of new diagnostic methodologies for vascular disease based on rapid, noninvasive, inexpensive simulation-assisted imaging. Additionally, this project will provide tools that could lead to new insight into the causes of aggressive plaque build-up in atherosclerotic arteries, into the genesis of atherosclerosis, and the forces that are involved in plaque rupture. The simulation tool will include automated construction of computational meshes from three-dimensional medical image scans or from three-dimensional reconstructions of Doppler ultrasound data. The numerical models will be based on adaptive, variable-order spectral element methods and will be designed to resolve the turbulent flow that results from stenoses (vessel narrowing), to predict vessel-wall motion due to fluctuating cardiac pressure. The experimental studies will be conducted using laser Doppler anemometry to validate the computational simulation tool. This vascular flow simulation tool will enable large patient-population studies that will help to quantify and gain fundamental insight to the role of hemodynamics in vascular disease.

Fluid Dynamics of Cerebral Spinal Fluid
Modeling of the Movement of Cerebrospinal Fluid

Francis Loth, Ph.D.
John Oshinski, Ph.D.
Paul Fischer, Ph.D.
Wojciech Kalata, M.S.
David Frim, M.D.
Richard Penn, M.D.
Atif Yardimci, Ph.D

Our group has developed expertise in various areas that provide valuable information about the geometric, flow, and pressure environment that exist within the spinal canal. We have developed a methodology of calculating a parameter that is representative of the unsteady resistance to CSF flow from the cranium to the subarachnoid space. This calculation is performed based the measured in vivo geometry and CSF flow rate obtained non-invasively using magnetic resonance imaging. We have computed this resistance parameter on two patients before and after surgery as well as on one healthy subject. The results show the unsteady resistance to decrease after decompression surgery, which is expected. However, we need to examine more cases in order to determine the clinical significance of the computed unsteady resistance parameter. We propose to perform the measurements and calculations on three more patients before and after surgery, which will provide further understanding of the clinical importance of the unsteady resistance parameter.

Importance of the Mechanical Forces in the Development of Syringomyelia for Patients With Chiari Malformation
Modeling of the Spinal Cord with a Syrinx

Francis Loth, Ph.D.
John Oshinski, Ph.D.
Wojciech Kalata, M.S.
Bryn Martin, B.S.

The overall goal is to better understand the mechanical forces, specifically pressure, that lead to the development of a syrinx in the spinal cord. The altered pressure environment after decompression surgery will be examined in order to better understand why this procedure is often successful in collapsing the syrinx. The proposed work consists of experiments on realistic syrinx models in which the unsteady pressure environment will be recorded to determine the mechanical forces (pressure environment) within and around the syrinx cavity as a function of time during the cardiac cycle. Model geometry and motion of cerebrospinal fluid (CSF) within the spinal canal will be based on patient data obtained using magnetic resonance (MR) imaging. A physical model of the spinal canal will be constructed to represent the in vivo geometry with syringomyelia. MR measurements will be made on this flow model to determine how well it mimics the real life case. The pressure measurements obtained inside this model will provide more information about the mechanical force environment within the spinal canal. This work will hopefully lead to a better understanding about why decompression surgery helps patients with syringomyelia. This, in turn, may lead to better surgical procedures for this disease.