Ultrathin-strut versus thin-strut stent healing and outcomes in preclinical and clinical subjects.

BACKGROUND: Compared with thin-strut durable-polymer drug-eluting stents (DP-DES), ultrathin-strut biodegradable-polymer sirolimus-eluting stents (BP-SES) improve stent-related clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Reduced stent strut thickness is hypothesised to underlie these benefits, but this conjecture remains unproven. AIMS: We aimed to assess the impact of strut thickness on stent healing and clinical outcomes between ultrathin-strut and thin-strut BP-SES. METHODS: First, we performed a preclinical study of 8 rabbits implanted with non-overlapping thin-strut (diameter/thickness 3.5 mm/80 µm) and ultrathin-strut (diameter/thickness 3.0 mm/60 µm) BP-SES in the infrarenal aorta. On day 7, the rabbits underwent intravascular near-infrared fluorescence optical coherence tomography (NIRF-OCT) molecular-structural imaging of fibrin deposition and stent tissue coverage, followed by histopathological analysis. Second, we conducted an individual data pooled analysis of patients enrolled in the BIOSCIENCE and BIOSTEMI randomised PCI trials treated with ultrathin-strut (n=282) or thin-strut (n=222) BP-SES. The primary endpoint was target lesion failure (TLF) at 1-year follow-up, with a landmark analysis at 30 days. RESULTS: NIRF-OCT image analyses revealed that ultrathin-strut and thin-strut BP-SES exhibited similar stent fibrin deposition (p=0.49) and percentage of uncovered stent struts (p=0.63). Histopathological assessments corroÂborated these findings. In 504 pooled randomised trial patients, TLF rates were similar for those treated with ultrathin-strut or thin-strut BP-SES at 30-day (2.5% vs 1.8%; p=0.62) and 1-year follow-up (4.3% vs 4.7%; p=0.88). CONCLUSIONS: Ultrathin-strut and thin-strut BP-SES demonstrate similar early arterial healing profiles and 30-day and 1-year clinical outcomes.

Intravascular Fluorescence Molecular Imaging of Atherosclerosis.

Optical molecular imaging using near-infrared fluorescence (NIRF) light is an emerging high-resolution imaging approach to image a wide range of molecular and cellular species in vivo. Imaging using NIR wavelengths (650-900 nm) enables deeper photon penetration into tissue and reduced tissue autofluorescence, resulting in higher sensitivity to detect exogenously administered NIR fluorophores (injectable molecular imaging agents). Greater imaging depth of several centimeters is further achievable in the NIR window as blood absorption is as an order of magnitude lower than in the visible range. Furthermore, as optical imaging is routinely performed in the cardiac catheterization laboratory (e.g., optical coherence tomography), intravascular NIRF offers a promising translational approach for clinical coronary and peripheral arterial imaging. To this point, the first human intravascular NIRF imaging study recently demonstrated the ability to detect NIR autofluorescence in patients with coronary atherosclerosis. This study provides a foundation for targeted intravascular NIRF molecular imaging studies in coronary patients. In this chapter, we detail system engineering, imaging agents and translational applications of intravascular NIRF molecular imaging.

Intravascular molecular-structural imaging with a miniaturized integrated near-infrared fluorescence and ultrasound catheter.

Coronary artery disease (CAD) remains a leading cause of mortality and warrants new imaging approaches to better guide clinical care. We report on a miniaturized, hybrid intravascular catheter and imaging system for comprehensive coronary artery imaging in vivo. Our catheter exhibits a total diameter of 1.0 mm (3.0 French), equivalent to standalone clinical intravascular ultrasound (IVUS) catheters but enables simultaneous near-infrared fluorescence (NIRF) and IVUS molecular-structural imaging. We demonstrate NIRF-IVUS imaging in vitro in coronary stents using NIR fluorophores, and compare NIRF signal strengths for prism and ball lens sensor designs in both low and high scattering media. Next, in vivo intravascular imaging in pig coronary arteries demonstrates simultaneous, co-registered molecular-structural imaging of experimental CAD inflammation on IVUS and distance-corrected NIRF images. The obtained results suggest substantial potential for the NIRF-IVUS catheter to advance standalone IVUS, and enable comprehensive phenotyping of vascular disease to better assess and treat patients with CAD.

Paclitaxel Drug-Coated Balloon Angioplasty Suppresses Progression and Inflammation of Experimental Atherosclerosis in Rabbits.

Paclitaxel drug-coated balloons (DCBs) reduce restenosis, but their overall safety has recently raised concerns. This study hypothesized that DCBs could lessen inflammation and reduce plaque progression. Using 25 rabbits with cholesterol feeding- and balloon injury-induced lesions, DCB-percutaneous transluminal angioplasty (PTA), plain PTA, or sham-PTA (balloon insertion without inflation) was investigated using serial intravascular near-infrared fluorescence-optical coherence tomography and serial intravascular ultrasound. In these experiments, DCB-PTA reduced inflammation and plaque burden in nonobstructive lesions compared with PTA or sham-PTA. These findings indicated the potential for DCBs to serve safely as regional anti-atherosclerosis therapy.

3D cellular-resolution imaging in arteries using few-mode interferometry.

Cross-sectional visualisation of the cellular and subcellular structures of human atherosclerosis in vivo is significant, as this disease is fundamentally caused by abnormal processes that occur at this scale in a depth-dependent manner. However, due to the inherent resolution-depth of focus tradeoff of conventional focusing optics, today's highest-resolution intravascular imaging technique, namely, optical coherence tomography (OCT), is unable to provide cross-sectional images at this resolution through a coronary catheter. Here, we introduce an intravascular imaging system and catheter based on few-mode interferometry, which overcomes the depth of focus limitation of conventional high-numerical-aperture objectives and enables three-dimensional cellular-resolution intravascular imaging in vivo by a submillimetre diameter, flexible catheter. Images of diseased cadaver human coronary arteries and living rabbit arteries were acquired with this device, showing clearly resolved cellular and subcellular structures within the artery wall, such as individual crystals, smooth muscle cells, and inflammatory cells. The capability of this technology to enable cellular-resolution, cross-sectional intravascular imaging will make it possible to study and diagnose human coronary disease with much greater precision in the future.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

Enhanced stokes and anti-stokes photoluminescence emission from LaAlO3:Nd+3 nanosized powder coated with a SiO2 shell layer.

The research on and development of materials in the field of rare-earth-ion doped nanocrystals for downconversion and up-conversion emission has been recognized to hold tremendous potential in the areas of photonic and biophotonic applications. In the present manuscript, the comprehensive results of the investigation of Stokes and anti-Stokes photoluminescence emission from the prepared LaAlO3:Nd+3 nanoparticles synthesized via the Pechini-type sol-gel method are presented and explained. The XRD diffraction peaks of the LaAlO3:Nd+3 nanoparticles can be easily assigned to the cubic-perovskite LaAlO3 structure. The FESEM image confirms the formation of approximately spherical particles within the range of 80 +/- 30 nm. The PL results showed that the LaAlO3 doped with 5% of Nd+3 ions shows the strongest emission. The core-shell structures obviously enhanced the photoluminescence intensity by suppressing the non-radiative emission and surface defects. As they yield the best PL measurement results, the LaAlO3:0.05Nd+3 nanoparticles were coated with a SiO2 shell layer, to enhance the photoluminescence emission. The mechanisms that are responsible for the photoluminescence emission process observed in the samples are discussed herein, with the help of the Nd+3 ion Dieke energy level diagram. Power dependence slope measurements were performed to identify the processes involved in the LaAlO3:Nd+3 up-conversion photoluminescence.

Effects of the nano-tubular anodic TiO2 buffer layer on bioactive hydroxyapatite coating.

We studied the effect of nano-tubular anodic TiO2 buffer layers on hydroxyapatite (HA) coating. The pulsed laser deposition (PLD) method was used to deposit HA on a well arranged nano-tubular anodic TiO2 (NT-ATO) buffer layer prepared by an electrochemical anodization technique. The surface morphology and chemical composition of HA coatings were characterized by using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and contact angle measurement. We found that crystalline HA coatings show well arranged porous morphologies with a favorable surface wettability. We also found that an anodic nano-tubular TiO2 buffer layer with a relatively short tube length shows a better coating morphology. The deposition process of HA on the nanotubular TiO2 buffer layer was also proposed.

Optical and electrical properties of ultralong ZnO nanorod fabricated from preheating hydrothermal method.

Ultralong ZnO nanorod arrays with a length of 10 microm were synthesized using a preheated hydrothermal-solution precursor, and their optical and electrical properties were studied using photoluminescence (PL) spectra and field effect transistors (FETs). The PL spectra showed ultraviolet, orange, and red emissions and had different temperature dependences with increasing temperature. The high-resolution photoluminescence spectra showed that the ultraviolet (UV) emission had different origins within different temperature ranges. The parameters describing the temperature dependence of the peak position shift, intensity, and full width at half maximum were evaluated using different models. After the fabrication of individual nanorod FETs, the ultralong ZnO NRs showed a clear n-type gate modulation with a typical electron concentration of 10(17) cm(-3) and a typical electron mobility of 35.7 cm2/V x s.