Infrared Spectroscopic Study and Mathematical Simulations of Carotid Atherosclerosis

Abstract

Background/aim: The pathogenesis, treatment and prevention of atherosclerosis continue to be the subject of intensive research and study by the scientific community. Based on Fourier-transform infrared spectra and 3D-Doppler echogram, we attempted to develop a computational simulation model for predicting the association of atherosclerotic risk factors with pathogenic molecular structural changes.

Materials and methods: Atheromatic carotid arteries from 56 patients (60-85 years old) were used as samples. Color 3D-Doppler echogram screening was performed on all patients preoperatively. Each infrared spectrum consisted of 120 co-added spectra at a spectral resolution of 4 cm^-1 Results: The infrared spectral analysis reveals 'marker bands', such as the 1,744 cm^-1 band assigned to aldehyde formation and to the 'fingerprint' digital spectral region of 1,050-1,169 cm^-1, characteristic of the presence of advanced glycation end products (C-O-C). The accumulation of calcium phosphate salts increases the formation rate of stenosis. The critical point of stenosis risk starts at about 45%, while when stenosis is over 60-70%, the risk of ischemic stroke or other major adverse cardiovascular events increases dramatically.

Conclusion: Fourier-transform infrared spectroscopy and mathematical simulation models showed that carotid artery stenosis over 45% reduces the blood flow rate, while stenosis over 65% dramatically increases the hemodynamic disturbance, with a parallel increase the rate of ischemic stroke or other major adverse cardiovascular events.

Keywords: 3D-Doppler echogram; FT-IR spectroscopy; blood flow; carotid atherosclerosis; mathematical simulations.

Figure 1. Representative Fourier-transform infrared spectra of a carotid atheromatic plaque. Spectrum a represents parts from a region rich in inorganic phase (calcified region). Spectrum b originates from the interfacial organometallic phase (calcium ions binding to organic molecules). Spectrum c shows the organic phase/inner membrane. Spectrum d corresponds to foam cells. Comparison between the spectra shows considerable differences in band absorption intensities, widths and shifts in all infrared spectral regions. AGEs: Advanced glycation end products; ACC: amorphous calcium carbonate.

Figure 2. A: Morphology of a representative carotid atheromatic plaque by scanning electron microscopy (100×, scale=500 μm). B: Elementary analysis of region B shown in A, rich in inorganic deposits. C: Elementary analysis of region C shown in A, rich in foam cells. D: ImageJ analysis of the linear calcified region D shown in A.

Figure 3. The geometry of the stenosed part of a carotid artery visualized as a cylindrical tube across the axis z with radial coordinates r. The disordered curve presents an arbitrary stenosed region 3lo/2, with α being the constant radius of the normal artery, d the non-stenosed part of the artery and R(z,t) is the radius of the stenosed region at real time t.

Figure 4. Computational simulation of blood flow (cm³/s) reduction over time between maximum systolic and maximum diastolic velocity is a function of atherosclerotic carotid artery stenosis. The inset shows an exemplary 3D-Doppler echogram from a patient with stenosis of 95% and peak systolic rate=441.5 cm/s, end-diastolic rate=69.8 cm/s. The curves show that after stenosis of between 73% to 95% there is no linear association with blood flow, increasing the risk of ischemic stroke event or death.

Figure 5. Relationship between blood flow (cm⁻³/s) and carotid artery stenosis. The curve is associated with ischemic stroke risk. The starting point of stroke risk for some patients is between 45% and 60% stenosis, while after 60%, the risk of ischemic stroke increases dramatically.