Interference-free Detection of Lipid-laden Atherosclerotic Plaques by 3D Co-registration of Frequency-Domain Differential Photoacoustic and Ultrasound Radar Imaging.

As lipid 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 modality that provides lipid-specific chemical information of 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 tissues also show some degree of absorption near 1210 nm and generate undesirable interfering PA signals. In this study, a novel wavelength-modulated Intravascular Differential Photoacoustic Radar (IV-DPAR) modality was introduced as an interference-free detection technique for a more accurate and reliable diagnosis of plaque progression. By using two low-power continuous-wave laser diodes in a differential manner, IV-DPAR could efficiently suppress undesirable absorptions and system noise, while dramatically improving system sensitivity and specificity to cholesterol, the primary ingredient of plaque necrotic core. When co-registered with intravascular ultrasound imaging, IV-DPAR could sensitively locate and characterize the lipid contents of plaques in human atherosclerotic arteries, regardless of their size and depth.

Review of the state of the art in cardiovascular endoscopy imaging of atherosclerosis using photoacoustic techniques with pulsed and continuous-wave optical excitations.

Intravascular photoacoustics (IV-PA) is an emerging atherosclerosis imaging modality that provides chemical-specific optical information of arterial walls with acoustic depth penetration and resolution. As lipid composition of atherosclerotic plaques is considered to be one of the primary indicators for plaque vulnerability, many IV-PA applications are calibrated so as to target plaque necrotic cores. Based on the mode of optical excitation and the corresponding signal processing technique, IV-PA is categorized into two different modalities. The pulse-based IV-PA has been the universal IV-PA imaging mode with its high peak power and straightforward time-domain signal processing technique. As an alternative, the low power continuous-wave (CW)-based IV-PA has been under intense development as a radar-like frequency-domain signal processing modality. The two state-of-the-art types of IV-PA are reviewed in terms of their physics and imaging capabilities, with major emphasis on frequency-swept CW-based IV-PA that has been recently introduced in the field.

Frequency-domain differential photoacoustic radar: theory and validation for ultrasensitive atherosclerotic plaque imaging.

Lipid composition of atherosclerotic plaques is considered to be highly related to plaque vulnerability. Therefore, a specific diagnostic or imaging modality that can sensitively evaluate plaques' necrotic core is desirable in atherosclerosis imaging. In this regard, intravascular photoacoustic (IVPA) imaging is an emerging plaque detection technique that provides lipid-specific chemical information from an arterial wall with great optical contrast and long acoustic penetration depth. While, in the near-infrared window, a 1210-nm optical source is usually chosen for IVPA applications since lipids exhibit a strong absorption peak at that wavelength, the sensitivity problem arises in the conventional single-ended systems as other arterial tissues also show some degree of absorption near that spectral region, thereby generating undesirably interfering photoacoustic (PA) signals. A theory of the high-frequency frequency-domain differential photoacoustic radar (DPAR) modality is introduced as a unique detection technique for accurate and molecularly specific evaluation of vulnerable plaques. By assuming two low-power continuous-wave optical sources at ∼1210 and ∼970 nm in a differential manner, DPAR theory and the corresponding simulation/experiment studies suggest an imaging modality that is only sensitive and specific to the spectroscopically defined imaging target, cholesterol.

The application of frequency-domain photoacoustics to temperature-dependent measurements of the Grüneisen parameter in lipids.

The Grüneisen parameter is an essential factor in biomedical photoacoustic (PA) diagnostics. In most PA imaging applications, the variation of the Grüneisen parameter with tissue type is insignificant. This is not the case for PA imaging and characterization of lipids, as they have a very distinct Grüneisen parameter compared with other tissue types. One example of PA applications involving lipids is the imaging and characterization of atherosclerotic plaques. Intravascular photoacoustic (IVPA) imaging is a promising diagnostic tool that can evaluate both plaque severity and composition. The literature for IVPA has mainly focused on using the difference in absorption coefficients between plaque components and healthy arterial tissues. However, the Grüneisen parameters for lipids and their behavior with temperature have not been well established in the literature. In this study we employ frequency-domain photoacoustic measurements to estimate the Grüneisen parameter by virtue of the ability of this modality to independently measure both the absorption coefficient and the Grüneisen parameter through the use of the phase channel. The values of the Grüneisen parameters of some lipids are calculated as functions of temperature in the range 25-45 °C.

Wavelength-modulated differential photoacoustic radar imager (WM-DPARI): accurate monitoring of absolute hemoglobin oxygen saturation.

Accurate monitoring of blood oxy-saturation level (SO2 ) in human breast tissues is clinically important for predicting and evaluating possible tumor growth at the site. In this work, four different non-invasive frequency-domain photoacoustic (PA) imaging modalities were compared for their absolute SO2 characterization capability using an in-vitro sheep blood circulation system. Among different PA modes, a new WM-DPAR imaging modality could estimate the SO2 with great accuracy when compared to a commercial blood gas analyzer. The developed WM-DPARI theory was further validated by constructing SO2 tomographic images of a blood-containing plastisol phantom.

Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS) for noninvasive early cancer detection and tissue hypoxia monitoring.

This study introduces a novel noninvasive differential photoacoustic method, Wavelength Modulated Differential Photoacoustic Spectroscopy (WM-DPAS), for noninvasive early cancer detection and continuous hypoxia monitoring through ultrasensitive measurements of hemoglobin oxygenation levels (StO2 ). Unlike conventional photoacoustic spectroscopy, WM-DPAS measures simultaneously two signals induced from square-wave modulated laser beams at two different wavelengths where the absorption difference between maximum deoxy- and oxy-hemoglobin is 680 nm, and minimum (zero) 808 nm (the isosbestic point). The two-wavelength measurement efficiently suppresses background, greatly enhances the signal to noise ratio and thus enables WM-DPAS to detect very small changes in total hemoglobin concentration (CHb ) and oxygenation levels, thereby identifying pre-malignant tumors before they are anatomically apparent. The non-invasive nature also makes WM-DPAS the best candidate for ICU bedside hypoxia monitoring in stroke patients. Sensitivity tunability is another special feature of the technology: WM-DPAS can be tuned for different applications such as quick cancer screening and accurate StO2 quantification by selecting a pair of parameters, signal amplitude ratio and phase shift. The WM-DPAS theory has been validated with sheep blood phantom measurements. Sensitivity comparison between conventional single-ended signal and differential signal.