Research

Research
Summary

Our research vision is to broadly apply engineering mechanics to address prevalent challenges in cardiovascular biology, physiology, and medicine. We seek to establish robust experimental and computational approaches to characterize the fluid and solid biomechanical environments in biologic soft tissues. Our primary objectives are to 1) advance the clinical diagnosis, prognosis, and treatment of cardiovascular disease and 2) elucidate mechanically sensitive biologic mechanisms for targeted drug therapies. In addition, we collaborate widely with scientists, engineers, clinicians, and clinical-scientists on a range of topics that seek to understand the role of mechanics in disease and medical device design.

We invite you to explore our research topic area and publications.

Topics

Coronary Artery Disease Progression

Coronary artery disease (CAD) is the leading cause of death worldwide. A significant clinical challenge in the treatment of CAD is identifying patients at risk for rapid disease progression and potential rupture of an atherosclerotic plaque (i.e., plaque rupture). As mechanical loads have been postulated to play a central role in the development and progression of atherosclerosis, which is the underlying CAD, we seek to understand better the role of biomechanics in the natural history of coronary atherosclerosis in longitudinal clinical investigations. Areas of focus include:

  • evaluation of fluid and solid mechanical loads on plaque progression, vulnerability, and rupture potential
  • establishing novel computational approaches to determine the material properties of coronary tissues and characterize the 3D mechanical environment in patient-specific models
  • application of uncertainty quantification (UQ) to patient-specific computational models
Timmins et al., J. R. Soc. Interface, 2017

Timmins et al., J. R. Soc. Interface, 2017.

Costopoulus et al., Eur. Heart J., 2019

Samady et al., Circulation, 2011.

Samady et al., Circulation, 2011.

Stented Artery Biomechanics

Vascular stent implantation is one of the most common major medical procedures provided by the US health care system for the treatment of coronary heart disease (~600,000 stents implanted annually). Periprocedural complications following these interventions continue with failure rates as high as 20% depending on disease complexity and stent platform. A major focus of our research is directed at developing pre-interventional and post-procedural optimization strategies guided by biomechanics and intravascular imaging. Areas of focus include:

  • developing novel computational approaches to quantify the mechanical interaction between vascular stents and arterial tissues
  • patient-specific modeling to characterize post-stent mechanical environment
  • establishing high-fidelity visualization strategies for deployed stents and surrounding tissue
  • pre-interventional and post-procedural optimization strategies

Elliott et al., IEEE Trans. Med. Imag., 2019

Timmins et al., Lab. Invest., 2011

Timmins et al., Lab. Invest., 2011

Evaluation of In Vivo Hemodynamics with Cardiac Magnetic Resonance Imaging

Four-dimensional flow cardiac magnetic resonance imaging (4D flow cMRI) provides a non-invasive, non-ionizing radiation-based diagnostic and prognostic tool to directly interrogate the in vivo hemodynamic environment. My lab has pioneered efforts to utilize 4D flow cMRI to quantify patient-specific wall shear stress (WSS), which is a measure of the force flowing blood exerts on the endothelial cells that line blood vessels. WSS has been linked to the development and progression of numerous cardiovascular diseases and thus has great potential in the clinical management of patients across a range of cardiovascular pathologies. Areas of focus include:

  • optimization of 4D flow cMRI acquisition, processing, and visualization strategies to advance the understanding of blood flow patterns
  • development of a novel approaches to quantify WSS directly from 4D flow cMRI
  • application of MR-derived hemodynamic metrics to define early indicators for vascular disease risk
Hurd et al., (under review)

Hurd et al., Cardiovasc. Eng. Technol., 2022

Extracellular Matrix Organization, Remodeling, and Damage in Fibrous Tissues

The extracellular matrix (ECM) is a 3D scaffold comprised of collagen, elastin, proteoglycans, and other proteins and minerals that supports the surrounding cells in biologic tissue. Among other key functions, the biomechanical and biochemical properties of the ECM have implications for several pathologies, including cancer, fibrosis, and cardiovascular disease. We have sought to establish methods to evaluate the structure-function relationship, organization, and remodeling of the ECM in tissues where altered ECM dynamics are involved in disease development. Areas of focus include:

  • application of nonlinear optical microscopy to identify structural inhomogeneity and fiber orientation in vascular tissue
  • targeting ECM damage for therapeutic potential
  • examining spatial and temporal changes in collagen and elastin organization with multiphoton imaging in a mouse model of atherosclerosis
Smith et al., Ann. Biomed. Eng., 2021

Smith et al., Ann. Biomed. Eng., 2021

Timmins et al., AJP Heart and Circ. Physiol., 2011

Timmins et al., AJP Heart and Circ. Physiol., 2011