In-vivo mechanical characterization of coronary atherosclerotic plaques in living swine using intravascular laser speckle imaging

Abstract

The ability to evaluate the viscoelastic properties of coronary arteries is crucial for identifying mechanically unstable atherosclerotic plaques. Here, we demonstrate for the first time in living swine, the capability of intravascular laser speckle imaging (ILSI) to measure an index of coronary plaque viscoelasticity, τ, using a human coronary to swine xenograft model. Cardiac motion effects are evaluated by comparing the EKG-non-gated ${\overline{\tau }}_{NG}$ , and EKG-gated ${\overline{\tau }}_G$ among different plaque types. Results show that both ${\overline{\tau }}_{NG}$ and ${\overline{\tau }}_G$ are significantly lower in necrotic-core plaques compared with stable lesions. Discrete-point pullback measurements demonstrate the capability of ILSI for rapid mechanical characterization of coronary segments under physiological conditions, in-vivo.

Fig. 1.

First generation prototype ILSI catheter. (a) The distal end of the catheter, incorporating the single-mode optical fiber (SM600), the GRIN lens, the polarizer and the rod mirror to illuminate the arterial wall (Scale bar: 1 mm). Arterial speckle patterns are collected through the slanted rod mirror, transmitted by a leached fiber optical bundle (SCHOTT, USA; OD 0.7mm; 4.5k fibers; partial core size 0.36), and captured by a high-speed CMOS triggerable camera (Mikrotron, Germany). (b) Custom-fabricated double lumen sheath, housing the ILSI catheter. The inner lumen accommodates the leached fiber bundle and the illumination fiber. The outer lumen incorporates a proximal occlusion balloon (maximum outer dia. 3 mm) and a flushing port to clear the blood from imaging FOV. Reprinted with permission (Ref. [21]).

Fig. 2.

Human coronary to live swine heart xenograft. A median sternotomy was performed to expose the beating heart of the anesthetized swine. The human xenograft was sutured to the anterior wall of the swine heart to simulate physiological motion. An aorto-atrial conduit redirected the blood flow to the grafted coronary via the first inlet of a Y connector. The second inlet allowed for the entrance of the ILSI catheter. A Doppler flowmeter monitored the blood stream redirected through the graft towards the right atrium. Arrow shows direction of blood from aorta (AO) to right atrium (RA). The ILSI catheter was housed in a double lumen sheath. The portable console was comprised of the He-Ne laser source and the bulk optics such as mirrors, beam expander, and fiber coupler (FC) for directing the light into the SMF. The arterial speckle patterns, imaged by the distal optics were transmitted by the fiber bundle to the high speed, triggerable CMOS camera. To generate the trigger signal, the EKG and femoral artery pressure waveforms were fed to a custom-made amplifier module. The amplified signals were digitized and processed by a data acquisition card (NI USB 6251 DAQ) incorporated in the console. The trigger pulse train was fed to the frame grabber for initiating the acquisition in synchrony with the pressure signal (Ref. [21]).

Fig. 3.

Speckle intensity autocorrelation curves, g₂(t), obtained for three coronary lesion groups, namely Fibrous/Fibrocalcific (FI/FC), Fibro-fatty (FA), and Necrotic Core Fibroatheroma (NCFA), using the EKG-gated and EKG-non-gated ILSI analyses. The g₂(t) curves corresponding to different plaque groups are substantially different. At the same time, the g₂(t) curves corresponding to the same plaque groups, evaluated using EKG-gated and Non-gated approaches correspond closely.

Fig. 4.

(a) The Speckle intensity decorrelation time, τ, evaluated by the ILSI catheter, in-vivo, using both non-gated and gated analysis, as the catheter is manually advanced to discrete arterial imaging sites. (b) The histology image corresponding to each location, along with the plaque type. It is clear that speckle decorrelation time varies in accordance with the arterial wall stability.

Fig. 5.

(a) The bar diagram representing the average in-vivo speckle decorrelation time constant at both non-gated random cardiac and gated mid-diastole phases, i.e.${\overline{\tau }}_{NG}$ and ${\overline{\tau }}_G$ for FI/FC, FA, and NCFA lesions. Error bars represent the standard errors of the means. (b) Analysis of variance and tabulated p-values from the multiple comparison analysis, representing the significance of statistical differences between different pairs of groups. Both ${\overline{\tau }}_{NG}$ and ${\overline{\tau }}_G$ are highly significantly lower in vulnerable NCFA compared to the stable FI/FC plaques. While not significant, they are also trending lower in NCFA compared to FA.