Intra-coronary plaque biomechanics

Autopsy studies in patients have revealed a type of coronary plaque, the thin cap fibroatheroma (TCFA) implicated at the site of culprit thrombi in >70% of patients who have succumbed to AMI. Technologies such as optical coherence tomography (OCT), intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS) provide important microstructural and compositional information related to the risk of rupture. Yet, the prediction of plaque rupture leading to AMI remains an elusive goal. This is because plaques with similar vulnerable morphologic features do not all possess an equal likelihood of rupture. For example, in 70% of patients with AMI, multiple TCFA’s are found without rupture at sites remote from the culprit plaque, and in ~20% of cases plaque rupture is observed in necrotic core (NC) lesions with thicker fibrous caps (>100µm) or calcific nodules. These findings call into question a detection paradigm that relies solely on morphologic criteria and highlight the need to augment morphologic findings with critical biomechanical metrics, in order to accurately assess the risk of plaque rupture.

During the pathogenesis of atherosclerosis, the mechanical properties of the plaque are altered by a complex milieu of hemodynamic and biochemical processes. The ultimate event of plaque rupture is a biomechanical failure that occurs when a plaque with severely compromised mechanical properties is unable to withstand loads exerted on it. Therefore, in order to identify plaques with the highest risk of rupture, it is essential to complement morphologic information provided by current technologies with quantitative indices of mechanical failure. Our lab is developing a multi-modal paradigm to predict the risk of plaque rupture leading to AMI. Our paradigm will complement microstructural information obtained from OCT and plaque burden measurements from IVUS with mechanical measurements obtained using intracoronary laser speckle rheology (LSR). We envision the accurate prediction of coronary thrombosis will enable the development of new therapeutic devices and treatments to stabilize vulnerable plaque and reduce the incidence of AMI in the future.

Laser Speckle Rheology (LSR) of coronary atherosclerosis

ILSR measures the mechanical properties of atherosclerotic plaques by evaluating the time-scale of intensity fluctuations from time-varying laser speckle patterns. In a viscoelastic medium, suspended particles undergo Brownian motion, which is directly related to the viscoelastic properties of the medium. Consequently, in TCFAs, because of the relatively low viscosity of the lipids, particles within a compliant necrotic core exhibit more rapid Brownian motion compared with stiffer fibrous regions of the plaque. Because scatterer motion causes a modulation of the laser speckle pattern, the measurement of temporal intensity variations provides information about the intrinsic viscoelastic properties of the plaque and can be used to determine plaque mechanical properties.

Intracoronary LSR

Omni-directional viewing through an intracoronary catheter:  Cutaway and fly-through views of a coronary test phantom evaluated using intracoronary LSR. The colors represent spatially-varying mechanical properties (blue – red : soft – stiff)

Omni-directional catheter assembly

Relevant Publications

Intraluminal laser speckle rheology using an omni-directional viewing catheter. Wang J, Hosoda M, Tshikudi DM, Hajjarian Z, Nadkarni SK. Biomed Opt Express. 2016 Dec 8;8(1):137-150. doi: 10.1364/BOE.8.000137. eCollection 2017 Jan 1. PMID: 28101407