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.

Correction: Label free localization of nanoparticles in live cancer cells using spectroscopic microscopy.

Correction for 'Label free localization of nanoparticles in live cancer cells using spectroscopic microscopy' by Graham L. C. Spicer et al., Nanoscale, 2018, 10, 19125-19130, https://doi.org/10.1039/C8NR07481J.

Noninvasive hemoglobin sensing and imaging: optical tools for disease diagnosis.

SIGNIFICANCE: Measurement and imaging of hemoglobin oxygenation are used extensively in the detection and diagnosis of disease; however, the applied instruments vary widely in their depth of imaging, spatiotemporal resolution, sensitivity, accuracy, complexity, physical size, and cost. The wide variation in available instrumentation can make it challenging for end users to select the appropriate tools for their application and to understand the relative limitations of different methods. AIM: We aim to provide a systematic overview of the field of hemoglobin imaging and sensing. APPROACH: We reviewed the sensing and imaging methods used to analyze hemoglobin oxygenation, including pulse oximetry, spectral reflectance imaging, diffuse optical imaging, spectroscopic optical coherence tomography, photoacoustic imaging, and diffuse correlation spectroscopy. RESULTS: We compared and contrasted the ability of different methods to determine hemoglobin biomarkers such as oxygenation while considering factors that influence their practical application. CONCLUSIONS: We highlight key limitations in the current state-of-the-art and make suggestions for routes to advance the clinical use and interpretation of hemoglobin oxygenation information.

Extended depth of focus by self-imaging wavefront division with the mirror tunnel.

The mirror tunnel is a component used to extend the depth of focus for compact imaging probes used in endoscopic optical coherence tomography (OCT). A fast and accurate method for mirror tunnel probe simulation, characterization, and optimization is needed, with the aim of reconciling wave- and ray-optics simulation methods and providing a thorough description of the physical operating principle of the mirror tunnel. BeamLab software, employing the beam propagation method, was used to explore the parameter space and quantify lateral resolution and depth of focus extension. The lateral resolution performance was found to depend heavily on the metric chosen, implying that care should be taken in the interpretation of optimization and simulation results. Interpreting the mirror tunnel exit face as an extended object gives an understanding of the probe operation, decoupling it from the focusing optics and potentially helping to reduce the parameter space for future optimization.

Harnessing DNA for nanothermometry.

Temperature measurement at the nanoscale has brought insight to a wide array of research interests in modern chemistry, physics, and biology. These measurements have been enabled by the advent of nanothermometers, which relay nanoscale temperature information through the analysis of their intrinsic photophysical behavior. In the past decade, several nanothermometers have been developed including dyes, nanodiamonds, fluorescent proteins, nucleotides, and nanoparticles. However, temperature measurement using intact DNA has not yet been achieved. Here, we present a method to study the temperature sensitivity of the DNA molecule within a physiologic temperature range when complexed with fluorescent dye. We theoretically and experimentally report the temperature sensitivity of the DNA-Hoechst 33342 complex in different sizes of double-stranded oligonucleotides and plasmids, showing its potential use as a nanothermometer. These findings allow for extending the thermal study of DNA to several research fields including DNA nanotechnology, optical tweezers, and DNA nanoparticles.

Universal guidelines for the conversion of proteins and dyes into functional nanothermometers.

In the last decade, technological advances in chemistry and photonics have enabled real-time measurement of temperature at the nanoscale. Nanothermometers, probes specifically designed to relay these nanoscale temperature changes, provide a high degree of temperature, temporal, and spatial resolution and precision. Several different approaches have been proposed, including microthermocouples, luminescence and fluorescence polarization anisotropy-based nanothermometers. Anisotropy-based nanothermometers excel in terms of biocompatibility because they can be built from endogenous proteins conjugated to dyes, minimizing any system perturbation. Moreover, the resulting fluorescent proteins can retain their native structure and activity while performing the temperature measurement, allowing precise temperature recordings from the native environment or during an enzymatic reaction in any given experimental system. To facilitate the future use of these nanothermometers in research, here we present a theoretical model that predicts the optimal sensitivity for anisotropy-based thermometers starting with any protein or dye, based on protein size and dye fluorescence lifetime. Using this model, most proteins and dyes can be converted to nanothermometers. The utilization of these nanothermometers by a broad spectrum of disciplines within the scientific community will bring new knowledge and understanding that today remains unavailable with current techniques.

Spectral contrast optical coherence tomography angiography enables single-scan vessel imaging.

Optical coherence tomography angiography relies on motion for contrast and requires at least two data acquisitions per pointwise scanning location. We present a method termed spectral contrast optical coherence tomography angiography using visible light that relies on the spectral signatures of blood for angiography from a single scan using endogenous contrast. We demonstrate the molecular sensitivity of this method, which enables lymphatic vessel, blood, and tissue discrimination.

Label free localization of nanoparticles in live cancer cells using spectroscopic microscopy.

Gold nanoparticles (GNPs) have become essential tools used in nanobiotechnology due to their tunable plasmonic properties and low toxicity in biological samples. Among the available approaches for imaging GNPs internalized by cells, hyperspectral techniques stand out due to their ability to simultaneously image and perform spectral analysis of GNPs. Here, we present a study utilizing a recently introduced hyperspectral imaging technique, live-cell PWS, for the imaging, tracking, and spectral analysis of GNPs in live cancer cells. Using principal components analysis, the extracellular or intracellular localization of the GNPs can be determined without the use of exogenous labels. This technique uses wide-field white light, assuring minimal toxicity and suitable signal-to-noise ratio for spectral and temporal resolution of backscattered signal from GNPs and local cellular structures. The application of live-cell PWS introduced here could make a great impact in nanomedicine and nanotechnology by giving new insights into GNP internalization and intracellular trafficking.

Single capillary oximetry and tissue ultrastructural sensing by dual-band dual-scan inverse spectroscopic optical coherence tomography.

Measuring capillary oxygenation and the surrounding ultrastructure can allow one to monitor a microvascular niche and better understand crucial biological mechanisms. However, capillary oximetry and pericapillary ultrastructure are challenging to measure in vivo. Here we demonstrate a novel optical imaging system, dual-band dual-scan inverse spectroscopic optical coherence tomography (D2-ISOCT), that, for the first time, can simultaneously obtain the following metrics in vivo using endogenous contrast: (1) capillary-level oxygen saturation and arteriolar-level blood flow rates, oxygen delivery rates, and oxygen metabolic rates; (2) spatial characteristics of tissue structures at length scales down to 30 nm; and (3) morphological images up to 2 mm in depth. To illustrate the capabilities of D2-ISOCT, we monitored alterations to capillaries and the surrounding pericapillary tissue (tissue between the capillaries) in the healing response of a mouse ear wound model. The obtained microvascular and ultrastructural metrics corroborated well with each other, showing the promise of D2-ISOCT for becoming a powerful new non-invasive imaging tool.

Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells.

Oxygen saturation ( sO 2 ) of red blood cells (RBCs) in capillaries can indirectly assess local tissue oxygenation and metabolic function. For example, the altered retinal oxygenation in diabetic retinopathy and local hypoxia during tumor development in cancer are reflected by abnormal sO 2 of local capillary networks. However, it is far from clear whether accurate label-free optical oximetry (i.e., measuring hemoglobin sO 2 ) is feasible from dispersed RBCs at the single capillary level. The sO 2 -dependent hemoglobin absorption contrast present in optical scattering signal is complicated by geometry-dependent scattering from RBCs. We present a numerical study of backscattering spectra from single RBCs based on the first-order Born approximation, considering practical factors: RBC orientations, size variation, and deformations. We show that the oscillatory spectral behavior of RBC geometries is smoothed by variations in cell size and orientation, resulting in clear sO 2 -dependent spectral contrast. In addition, this spectral contrast persists with different mean cellular hemoglobin content and different deformations of RBCs. This study shows for the first time the feasibility of, and provides a theoretical model for, label-free optical oximetry at the single capillary level using backscattering-based imaging modalities, challenging the popular view that such measurements are impossible at the single capillary level.

Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo.

The onset of distant organ metastasis from primary breast cancer marks the transition to a stage IV diagnosis. Standard imaging modalities often detect distant metastasis when the burden of disease is high, underscoring the need for improved methods of detection to allow for interventions that would impede disease progression. Here, microporous poly(ε-caprolactone) scaffolds were developed that capture early metastatic cells and thus serve as a sentinel for early detection. These scaffolds were used to characterize the dynamic immune response to the implant spanning the acute and chronic foreign body response. The immune cell composition had stabilized at the scaffold after approximately 1 month and changed dramatically within days to weeks after tumor inoculation, with CD11b(+)Gr1(hi)Ly6C(-) cells having the greatest increase in abundance. Implanted scaffolds recruited metastatic cancer cells that were inoculated into the mammary fat pad in vivo, which also significantly reduced tumor burden in the liver and brain. Additionally, cancer cells could be detected using a label-free imaging modality termed inverse spectroscopic optical coherence tomography, and we tested the hypothesis that subsequent removal of the primary tumor after early detection would enhance survival. Surgical removal of the primary tumor following cancer cell detection in the scaffold significantly improved disease-specific survival. The enhanced disease-specific survival was associated with a systemic reduction in the CD11b(+)Gr1(hi)Ly6C(-) cells as a consequence of the implant, which was further supported by Gr-1 depletion studies. Implementation of the scaffold may provide diagnostic and therapeutic options for cancer patients in both the high-risk and adjuvant treatment settings. Cancer Res; 76(18); 5209-18. ©2016 AACR.

Detection of extracellular matrix modification in cancer models with inverse spectroscopic optical coherence tomography.

In cancer biology, there has been a recent effort to understand tumor formation in the context of the tissue microenvironment. In particular, recent progress has explored the mechanisms behind how changes in the cell-extracellular matrix ensemble influence progression of the disease. The extensive use of in vitro tissue culture models in simulant matrix has proven effective at studying such interactions, but modalities for non-invasively quantifying aspects of these systems are scant. We present the novel application of an imaging technique, Inverse Spectroscopic Optical Coherence Tomography, for the non-destructive measurement of in vitro biological samples during matrix remodeling. Our findings indicate that the nanoscale-sensitive mass density correlation shape factor D of cancer cells increases in response to a more crosslinked matrix. We present a facile technique for the non-invasive, quantitative study of the micro- and nano-scale structure of the extracellular matrix and its host cells.

Finite-difference time-domain-based optical microscopy simulation of dispersive media facilitates the development of optical imaging techniques.

Combining finite-difference time-domain (FDTD) methods and modeling of optical microscopy modalities, we previously developed an open-source software package called Angora, which is essentially a "microscope in a computer." However, the samples being simulated were limited to nondispersive media. Since media dispersions are common in biological samples (such as cells with staining and metallic biomarkers), we have further developed a module in Angora to simulate samples having complicated dispersion properties, thereby allowing the synthesis of microscope images of most biological samples. We first describe a method to integrate media dispersion into FDTD, and we validate the corresponding Angora dispersion module by applying Mie theory, as well as by experimentally imaging gold microspheres. Then, we demonstrate how Angora can facilitate the development of optical imaging techniques with a case study.