Intravascular photoacoustic imaging (IVPA) can obtain specific inflammation information and lipid composition in vivo, which is a new method for the diagnosis of atherosclerotic plaques. Numerous IVPA systems have been proposed and pushed towards clinical application. But imaging speed hinders their final clinical translation, considering necessary blood flush or balloon blood blockage operations during the intravascular intervention. In this study, we developed a high-speed IVPA system based on a 1064 nm pulsed laser, with the imaging speed of 60 round/second, about twice speed of the fastest IVPA system. In this system, a 0.9 mm outer diameter catheter was used for simultaneous IVPA and IVUS imaging. A plastic tube with an outer diameter of 1.3 mm was wrapped on the outside of the imaging catheter for protection and blood flushing channels. Firstly, the capability of high-speed imaging was verified by the imaging of a manually moving metal needle. Photoacoustic and ultrasonic images of the needle were obtained. No artifacts were found during the real-time imaging of the needle, which was unavoidable in the low-speed imaging system. Then, an artery excised from abdominal aorta of a New Zealand rabbit was sealed and a certain frequency of flowing water was injected from the one end to simulate the pulsation of blood vessels with a frequency of about 4.5 Hz, which was a typical heart rate of a rabbit. The high-speed IVPA-US imaging of pulsed blood vessels was successfully performed, which proved the feasibility of the system in vivo and even further clinical application.
Carotid arteries are important channels delivering blood and oxygen to brain. Atherosclerosis plaque in carotid arteries hinders blood delivery, and plaque rupture causes stroke, leading to high morbidity and motility. Extensive preclinical and clinical studies showed that atherosclerosis inflammation activities are highly related to plaque vulnerability. Thus, visualizing the inflammation of atherosclerosis plaques is important in atherosclerosis vulnerability assessment. In this study, photoacoustic imaging modality was applied for carotid atherosclerosis inflammation identification of mouse in vivo. Deficient apolipoprotein E (ApoE-/-) mice with high-fat diet and normal diet for 16 weeks were employed as atherosclerosis models and control models, respectively. Photoacoustic molecular probes with optical absorption at nearinfrared wavelength and specifically target cluster of differentiation 36 (CD36) were employed to mark inflammation cells in carotid atherosclerosis plaques of mouse in vivo. Noninvasive imaging of atherosclerosis inflammation cells marked by molecular probes was performed by point-to-point scanning with a custom-built acoustic-resolution photoacoustic imaging system. Considering low scattering of near-infrared light in tissues and mature commercialization of laser, excitation wavelength in this research is chosen at 1064 nm. Carotid arteries with and without atherosclerosis plaques have been noninvasively imaged and distinguished. Furthermore, carotid atherosclerosis with different inflammation severity has been analyzed by photoacoustic imaging and immunohistochemistry staining. Photoacoustic signal from atherosclerosis arteries showed high relativity with inflammation severity defined by immunohistochemistry staining, evidencing the reliability of the novel imaging technology in atherosclerosis inflammation identification. This study paves the way for photoacoustic imaging technology to atherosclerosis inflammation identification, severity quantification and even further atherosclerosis therapy.
The optimal photoacoustic probe design is the key to obtain highest imaging sensitivity in photoacoustic computed tomography. Two commonly used probe design types are dark- and bright-field designs. We proposed a design for photoacoustic probe called quasibright-field illumination and compared the performance of all three kinds of probes theoretically and experimentally. Our conclusion is that the proposed quasibright-field illumination photoacoustic probe is superior compared to the existing probe designs as demonstrated. However, each type of illumination should still have its own advantages under certain circumstances. The dark-field illumination is capable of minimizing surface interference signals and reducing their contributions to the background of deeper signals. Hence, it should perform better when imaging samples with high optical absorbance at the surface layer. The bright field may perform better under circumstance when phase distortion is less. We also designed and fabricated three kinds of probes using a single multimode optical fiber for laser energy delivery instead of fiber bundle. Single fiber probes are low cost, transmit laser energy efficiently, and are compact for easy handling. Thus, our study not only provides a method for probe design but also a guidance for cost-effective transducer array-based photoacoustic probe design and manufacturing in the future.
KEYWORDS: Transducers, Photoacoustic tomography, Acoustics, Signal detection, Imaging systems, Signal to noise ratio, Data acquisition, Quartz, Ultrasonics, Sensors
A dual-foci transducer with coplanar light illumination and acoustic detection was applied for the first time. It overcame the small directivity angle, low-sensitivity, and large datasets in conventional circular scanning or array-based photoacoustic computed tomography (PACT). The custom-designed transducer is focused on both the scanning plane with virtual-point detection and the elevation direction for large field of view (FOV) cross-sectional imaging. Moreover, a coplanar light illumination and acoustic detection configuration can provide ring-shaped light irradiation with highly efficient acoustic detection, which in principle has a better adaptability when imaging samples of irregular surfaces. Phantom experiments showed that our PACT system can achieve high resolution (∼0.5 mm), enhanced signal-to-noise ratio (16-dB improvement), and a more complete structure in a greater FOV with an equal number of sampling points compared with the results from a flat aperture transducer. This study provides the proof of concept for the fabrication of a sparse array with the dual-foci property and large aperture size for high-quality, low-cost, and high-speed photoacoustic imaging.
For the diagnosis and evaluation of ophthalmic diseases, imaging and quantitative characterization of vasculature in the iris are very important. The recently developed photoacoustic imaging, which is ultrasensitive in imaging endogenous hemoglobin molecules, provides a highly efficient label-free method for imaging blood vasculature in the iris. However, the development of advanced vascular quantification algorithms is still needed to enable accurate characterization of the underlying vasculature. We have developed a vascular information quantification algorithm by adopting a three-dimensional (3-D) Hessian matrix and applied for processing iris vasculature images obtained with a custom-built optical-resolution photoacoustic imaging system (OR-PAM). For the first time, we demonstrate in vivo 3-D vascular structures of a rat iris with a the label-free imaging method and also accurately extract quantitative vascular information, such as vessel diameter, vascular density, and vascular tortuosity. Our results indicate that the developed algorithm is capable of quantifying the vasculature in the 3-D photoacoustic images of the iris in-vivo, thus enhancing the diagnostic capability of the OR-PAM system for vascular-related ophthalmic diseases in vivo.
Intravascular spectroscopic photoacoustic technology can image atherosclerotic plaque composition with high sensitivity and specificity, which is critical for identifying vulnerable plaques. Here, we designed and engineered a catheter of 0.9 mm in diameter for intravascular photoacoustic (IVPA) imaging, smaller than the critical size of 1 mm required for clinical translation. Further, a quasifocusing photoacoustic excitation scheme was developed for the catheter, producing well-detectable IVPA signals from stents and lipids with a laser energy as low as ∼30 μJ/pulse. As a result, this design enabled the use of a low-energy, high-repetition rate, ns-pulsed optical parametric oscillator laser for high-speed spectroscopic IVPA imaging at both the 1.2-μm and 1.7-μm spectral bands for lipid detection. Specifically, for each wavelength, a 1-kHz IVPA A-line rate was achieved, ∼100-fold faster than previously reported IVPA systems offering a similar wavelength tuning range. Using the system, spectroscopic IVPA imaging of peri-adventitial adipose tissue from a porcine aorta segment was demonstrated. The significantly improved imaging speed, together with the reduced catheter size and multiwavelength spectroscopic imaging ability, suggests that the developed high-speed IVPA technology is of great potential to be further translated for in vivo applications.
Intravascular ultrasound (IVUS) plays a vital role in assessing the severity of atherosclerosis and has greatly enriched our knowledge on atherosclerotic plaques. However, it mainly reveals the structural information of plaques. In contrast, spectroscopic and molecular photoacoustic imaging can potentially improve plaque composition identification, inflammation detection, and ultimately the stratification of plaque vulnerability and risk. In this work, we developed an integrated intravascular ultrasound and optical-resolution photoacoustic microscopy (IVUS-PAM) system with a single catheter as small as 1 mm in diameter, comparable to that of existing clinical IVUS catheters. In addition, by using a GRIN lens to focus the excitation laser pulse, the system provides an optical-diffraction limited photoacoustic lateral resolution as fine as 19.6 micrometers, ~10-fold finer than that of conventional intravascular photoacoustic imaging and existing IVUS technology. The system employs a custom-made miniaturized single-element ultrasonic transducer with a dimension of ~0.5 mm, a centre frequency of ~40 MHz, and a fractional bandwidth of ~60%. The IVUS-PAM can simultaneously acquire co-registered IVUS images with an axial resolution of ~40 micrometers and a lateral resolution of ~200 micrometers. In the future, IVUS-PAM may open up new opportunities for improved high-resolution vulnerable plaque imaging and image-guided stent deployment.
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