Zhonglie Piao

High speed intravascular photoacoustic imaging with fast optical parametric oscillator laser at 1.7 μm

Intravascular photoacoustic imaging at 1.7 μm spectral band has shown promising capabilities for lipid-rich vulnerable atherosclerotic plaque detection. In this work, we report a high speed catheter-based integrated intravascular photoacoustic/intravascular ultrasound (IVPA/IVUS) imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A lipid-mimicking phantom and atherosclerotic rabbit abdominal aorta were imaged at 1 frame per second, which is two orders of magnitude faster than previously reported in IVPA imaging with the same wavelength. Clear photoacoustic signals by the absorption of lipid rich deposition demonstrated the ability of the system for high speed vulnerable atherosclerotic plaques detection.

Label-free optical-resolution photoacoustic microscopy of superficial microvasculature using a compact visible laser diode excitation

We have developed laser-diode-based optical-resolution photoacoustic microscopy (LD-OR-PAM) of superficial microvasculature which has the desirable properties of being compact, low-cost, and label-free. A 300-mW visible pulsed laser diode was operated at a 405 ± 5 nm wavelength with a pulse energy as low as 52 nJ. By using a 3.6 MHz ultrasound transducer, the system was tested on carbon fibers with a lateral resolution of 0.95 µm and an SNR of 38 dB. The subcutaneous microvasculature on a mouse back was imaged without an exogenous contrast agent which demonstrates the potential of the proposed prototype for skin chromophores. Our eventual goal is to offer a practical and affordable multi-wavelength functional LD-OR-PAM instrument suitable for clinical applications.

In vivo microvascular network imaging of the human retina combined with an automatic three-dimensional segmentation method

Abstract. Microvascular network of the retina plays an important role in diagnosis and monitoring of various retinal diseases. We propose a three-dimensional (3-D) segmentation method with intensity-based Doppler variance (IBDV) based on swept-source optical coherence tomography. The automatic 3-D segmentation method is used to obtain seven surfaces of intraretinal layers. The microvascular network of the retina, which is acquired by the IBDV method, can be divided into six layers. The microvascular network of the six individual layers is visualized, and the morphology and contrast images can be improved by using the segmentation method. This method has potential for earlier diagnosis and precise monitoring in retinal vascular diseases.

Ultrafast optical-ultrasonic system and miniaturized catheter for imaging and characterizing atherosclerotic plaques in vivo

Atherosclerotic coronary artery disease (CAD) is the number one cause of death worldwide. The majority of CAD-induced deaths are due to the rupture of vulnerable plaques. Accurate assessment of plaques is crucial to optimize treatment and prevent death in patients with CAD. Current diagnostic techniques are often limited by either spatial resolution or penetration depth. Several studies have proved that the combined use of optical and ultrasonic imaging techniques increase diagnostic accuracy of vulnerable plaques. Here, we introduce an ultrafast optical-ultrasonic dual-modality imaging system and flexible miniaturized catheter, which enables the translation of this technology into clinical practice. This system can perform simultaneous optical coherence tomography (OCT)-intravascular ultrasound (IVUS) imaging at 72 frames per second safely in vivo, i.e., visualizing a 72 mm-long artery in 4 seconds. Results obtained in atherosclerotic rabbits in vivo and human coronary artery segments show that this ultrafast technique can rapidly provide volumetric mapping of plaques and clearly identify vulnerable plaques. By providing ultrafast imaging of arteries with high resolution and deep penetration depth simultaneously, this hybrid IVUS-OCT technology opens new and safe opportunities to evaluate in real-time the risk posed by plaques, detect vulnerable plaques, and optimize treatment decisions.

Lens-free endoscopy probe for optical coherence tomography

We present an ultrathin fiber-optic endoscopy probe for optical coherence tomography (OCT), which is made of a series of fused optical fibers instead of the conventional scheme based on an objective lens. The large-core fiber with a core diameter of 20 μm was utilized for the probe, while a single-mode fiber of core diameter 8.2 μm mainly delivered the OCT light. Those fibers were spliced with a bridge fiber of an intermediate core size. The guided light was stepwise converted to a beam of a large mode-field diameter to be radiated with a larger depth of focus. We obtained a 125 μm thick all-fiber endoscopy probe with a side-viewing capability implemented by an angled fiber end. Successful OCT imaging was demonstrated with a swept-source OCT system and showed the practical applicability of our lens-free endoscopy probe.

Q-switched Erbium-doped fiber laser at 1600 nm for photoacoustic imaging application

We present a nanosecond Q-switched Erbium-doped fiber (EDF) laser system operating at 1600 nm with a tunable repetition rate from 100 kHz to 1 MHz. A compact fiber coupled, acousto-optic modulator-based EDF ring cavity was used to generate a nanosecond seed laser at 1600 nm, and a double-cladding EDF based power amplifier was applied to achieve the maximum average power of 250 mW. In addition, 12 ns laser pulses with the maximum pulse energy of 2.4 μJ were obtained at 100 kHz. Furthermore, the Stokes shift by Raman scattering over a 25 km long fiber was measured, indicating that the laser can be potentially used to generate the high repetition rate pulses at the 1.7 μm region. Finally, we detected the photoacoustic signal from a human hair at 200 kHz repetition rate with a pulse energy of 1.2 μJ, which demonstrates that a Q-switched Er-doped fiber laser can be a promising light source for the high speed functional photoacoustic imaging.

In vivo photoacoustic monitoring using 700-nm region Raman source for targeting Prussian blue nanoparticles in mouse tumor model

Photoacoustic imaging (PAI) is a noninvasive imaging tool to visualize optical absorbing contrast agents. Due to high ultrasonic resolution and superior optical sensitivity, PAI can be used to monitor nanoparticle-mediated cancer therapy. The current study synthesized Food and Drug Administration-approved Prussian blue (PB) in the form of nanoparticles (NPs) with the peak absorption at 712 nm for photoacoustically imaging tumor-bearing mouse models. To monitor PB NPs from the background tissue in vivo, we also developed a new 700-nm-region stimulated Raman scattering (SRS) source (pulse energy up to 200 nJ and repetition rate up to 50 kHz) and implemented optical-resolution photoacoustic microscopy (OR-PAM). The SRS-assisted OR-PAM system was able to monitor PB NPs in the tumor model with micrometer resolution. Due to strong light absorption at 712 nm, the developed SRS light yielded a two-fold higher contrast from PB NPs, in comparison with a 532-nm pumping source. The proposed laser source involved cost-effective and simple system implementation along with high compatibility with the fiber-based OR-PAM system. The study highlights the OR-PAM system in conjunction with the tunable-color SRS light source as a feasible tool to assist NP-mediated cancer therapy.

Carbon Dots Doped with Dysprosium: A Bimodal Nanoprobe for MRI and Fluorescence Imaging

In recent years, functional nanoprobes with multiple imaging modalities have become an emerging field of biomedical research. In this preliminary study, we utilized a facile hydrothermal method for the preparation of magneto-fluorescent bimodal carbon dots doped with dysprosium (Dy-CDs). The prepared Dy-CDs have shown a good colloidal stability in a water solution and strong blue–green fluorescence, with a maximum at 452 nm. In addition, the excellent transverse relaxivity of the prepared Dy-CDs (r2 = 7.42 ± 0.07 mM−1s−1) makes them also suitable for T2-weighted magnetic resonance imaging (MRI). Thus, synthesized Dy-CDs could be potentially utilized for both MRI and fluorescence imaging of living cells.

Absence of adventitial vasa vasorum formation at the coronary segment with myocardial bridge - An optical coherence tomography study

BACKGROUND Myocardial bridge (MB) is a myocardial bundle through which coronary segment tunnels and could compress coronary arteries causing myocardial ischemia. However, the characteristic structural findings of MB remain to be fully elucidated. Recently, we demonstrated that optical coherence tomography (OCT) enables us to visualize adventitial vasa vasorum (VV) formation in humans. In this study, we examined adventitial VV formation at the coronary segment with MB in humans using OCT. METHODS We examined 15 consecutive patients with suspected angina pectoris and MB in the left anterior descending (LAD) coronary arteries but no angiographic coronary stenosis. MB was detected on coronary angiography as a segment with milking effect. We performed intracoronary OCT imaging along the entire LAD. Morphometric analysis was performed at MB and proximal/distal segments at every 1mm. RESULTS OCT examination showed the absence of adventitial VV formation at MB in the LAD, while VV was clearly noted at both the proximal and distal reference segments. Adventitial VV area was significantly less at MB compared with the proximal or distal references. CONCLUSIONS These results with OCT imaging indicate that coronary segments with MB lack adventitial VV formation in humans, suggesting that MB could influence morphological and functional changes of the coronary artery.

Cellular-resolution, extended depth of focus optical coherence tomography catheter toward in vivo cardiovascular imaging (Conference Presentation)

Optical coherence tomography (OCT) has been a useful clinical tool for diagnosing coronary artery disease through a flexible catheter, but its full promise relies on resolving cellular and sub-cellular structures in vivo. Previously, visualizing cellular structures through an imaging catheter is not possible due to limited depth of focus (DOF) of a tightly focused Gaussian beam: typically, a Gaussian beam with 2-3 μm resolution has a DOF within 100 μm, which is not sufficient for in vivo catheter imaging. Therefore, we developed a self-imaging wavefront division optical system that generates a coaxially-focused multimode (CAFM) beam with a DOF that is approximately one order of magnitude longer than that of a Gaussian beam. In this study, we present a high-resolution, extended DOF catheter based on self-imaging wavefront division optics. The catheter generates a CAFM beam with a lateral resolution of 3 μm and a DOF close to 2 mm. To correct the aberration introduced by catheter sheath, we incorporated a cylindrical prism to compensate the sheath astigmatism. When the catheter is incorporated into a micro-resolution OCT (μOCT) system with rotational scanning mechanics, cellular-resolution cross-sectional images of the coronary artery wall can be obtained. The device serves as an important step toward characterizing cellular and sub-cellular structures in vivo for coronary artery disease diagnosis.