23 Mar 2021
Wellman Center imaging technique could help identify arterial plaques most likely to rupture.
Methods used to try and assess the physical properties of plaque in vivo have included OCT and photoacoustic radar, but a way to measure the key mechanical factors and viscoelastic parameters has proved elusive.
"Measurement of the plaque mechanical properties is crucial in identifying unstable plaques with a propensity for rupture and subsequent heart attack," said Seemantini Nadkarni of the Wellman Center. "ILSI provides the unique capability to quantify an index of mechanical properties of coronary plaques, thus providing a direct assessment of mechanical stability."
First attempts to use laser speckle as a means to investigate arterial plaque were made at the Wellman Center back in 2005, exploiting the way that interference between photons returning from different regions within the tissue resulted in a granular intensity pattern on the tissue surface.
These temporal intensity variations could provide information about the intrinsic viscoelastic properties of the plaque, but for an effective clinical technique a number of practical issues relating to transmission of the speckle pattern to an image detector in the presence of cardiac motion had to be tackled.
Another key challenge involved the influence of inter-fiber leakage of light during movement of the fiber bundle on the accuracy of the recorded speckle data.
The Wellman Center has addressed these issues by designing a new instrument, a "small diameter intravascular catheter that incorporates an optical fiber that delivers light to the coronary artery wall," said Nadkarni. "We also used a small-diameter fiber bundle, polarizer and gradient-index (GRIN) lens to image the reflected speckle patterns from the arterial wall onto a CMOS sensor."
The new device was tested using a human coronary to swine xenograft model, in which a section of human blood vessel is grafted to the heart of a pig.
"This represents the next major stride in the clinical translational journey for ILSI," commented the project in its paper. "We evaluated the capability of ILSI to perform intravascular assessment of human coronary plaques under in vivo physiological conditions of cardiac and respiratory motion."
Exquisite diagnostic sensitivity
A protocol was developed comparing image acquisition triggered by the EKG signal of the beating heart with non-EKG-gated signals, to assess the dynamic effects of cardiac motion on the speckle data. A parameter termed the speckle decorrelation time constant was then calculated, as a measure of how the speckle pattern intrinsic to the plaque itself progressed in the image frames immediately after illumination.
Results showed that this parameter was significantly lower for necrotic-core plaques of the kind must likely to rupture than it was for more stable lesions.
"The time constants in unstable plaques were significantly and distinctly lower than other stable plaques in the coronary wall," said Nadkarni. "These results demonstrated the exquisite diagnostic sensitivity and specificity of ILSI for detecting human lipid pool plaques that were most likely to rupture under physiological conditions."
One clinical advantage of the ILSI platform may be the ability to easily integrate it with the established intracoronary technologies such as OCT or ultrasound, combining the mechanical data from ILSI with morphological information to improve the evaluation of plaque stability.
The next steps will involve further preclinical studies in live animals, prior to assessment of the safety of the ILSI catheter for use in humans as a step towards ultimate clinical use.
"Tissue mechanical assessment using ILSI in vivo marks a critical milestone for speckle-based mechanical characterization technologies at large, by opening new avenues for the diagnosis of thromboembolic conditions in both coronary and peripheral arteries," said the project.