Wavelength-modulated Intravascular Differential Photoacoustic Radar for Interference-free Detection of Vulnerable Plaques in Atherosclerosis

As lipid (or cholesterol) composition of atherosclerotic plaques is considered to be one of the primary indicators for plaque vulnerability, a diagnostic modality that can sensitively evaluate their necrotic core is highly desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection technique that provides lipid-specific chemical information of diseased arterial walls. Within the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications because lipid exhibits a strong absorption peak at that wavelength. However, other arterial chromophores also show some degree of absorption near 1210 nm and generate undesirably interfering PA signals upon the same optical excitation. In this study, a novel wavelength-modulated differential photoacoustic radar (IV-DPAR) modality was introduced as an interference-free lipid detection technique for a more accurate and reliable diagnosis of plaque progression. Unlike mainstream IVPA modalities that are based on pulsed optical sources, IV-DPAR utilizes low-power intensity-modulated continuous-wave (CW) laser diodes for optical excitation. With frequency-swept optical modulation and the matched-filter pulse compression processing, IV-DPAR was demonstrated to perform spatially-resolved functional imaging on lipids with excellent signal-to-noise ratio (SNR). Signal processing algorithms were investigated to explore the novel phase-filtered amplitude (PFA) channel. By encoding the phase-derived statistical probability of the presence of lipids on the conventional amplitude channel, the PFA channel could significantly enhance various imaging parameters such as SNR and axial resolution. Most importantly, the simultaneous modulation of the two CW lasers in IV-DPAR facilitated the unique differential dual-waveform engineering technique that could efficiently suppress undesirable background absorptions and system noise to approximately zero baselines, while dramatically improving detection sensitivity and specificity toward lipids, the primary ingredient of a plaque necrotic core. When co-registered with clinically-accepted intravascular ultrasound imaging, IV-DPAR could not only locate but also quantitatively characterize the lipid contents of plaques in porcine and human atherosclerotic arteries, regardless of their size and depth.Ph.D