AIMS Percutaneous revascularisation of chronic total occlusions (CTO) is limited by failure of guidewire crossing. Neovascularisation within the proximal CTO segment may be important for guidewire crossing and dramatically declines in CTO beyond six weeks of age. The aims of the current study were to determine whether local delivery of a pro-angiogenic growth factor increases neovascularisation in mature CTO and facilitates guidewire crossings. METHODS AND RESULTS CTO (n=51) were created in the femoral arteries of 44 New Zealand white rabbits using the thrombin injection model. At 12 weeks, CTO were treated with poly-lactic-glycolic-acid (PLGA) microspheres containing either bovine serum albumin (BSA) (n=15) or recombinant mouse VEGF164 (n=14), or received no intervention (controls, n=12). Contrast-enhanced magnetic resonance angiography (CEMRA) was performed prior to treatment and at three weeks post treatment. Animals were sacrificed at three weeks post treatment and arterial samples were excised for micro-computed tomography imaging (µCT) and histologic morphometric analysis. Guidewire crossing was assessed at three weeks post treatment in an additional 10 VEGF164-treated CTO. In comparison to BSA-treated and control non-intervened CTO, VEGF164-treated CTO showed a significant increase in relative blood volume index in the proximal segment of the CTO lesion as determined by CEMRA and by µCT. Histologic measurements of microvessel area were also higher in VEGF164-treated CTO. Guidewire crossing across the proximal fibrous cap was successful in eight out of 10 VEGF164-treated CTO. CONCLUSIONS Angiogenic therapy appears to be a promising strategy to improve neovascularisation and guidewire crossing rates in CTO.

A prototype intraoperative hand-held optical coherence tomography (OCT) imaging probe was developed to provide micron resolution cross-sectional images of subsurface tissue during open surgery. This new ergonomic probe was designed based on electrostatically driven optical fibers, and packaged into a catheter probe in the form factor of clinically accepted Bayonet shaped neurosurgical probes. Optical properties of the probe were measured to have a ~20 μm spot size, 5 mm working distance and 4 mm field of view. Feasibility of this probe for structural and Doppler shift imaging was tested on porcine femoral blood vessel imaging.

AIMS:To create a large animal coronary chronic total occlusion (CTO) model. Presence of microvessels within the CTO lumen facilitates guidewire crossing. The patterns and time profiles of matrix changes and microvessel formation during coronary CTO maturation are unknown.METHODS AND RESULTS:CTO were created in 15 swine by percutaneous deployment of a collagen plug. Matrix changes were assessed by histology. Intraluminal neovascularisation was assessed by histology and several imaging modalities, including conventional and 3D spin angiography, micro-computed tomography (micro-CT) imaging, and contrast-enhanced magnetic resonance imaging (MRI), at six and 12 weeks following CTO creation. Matrix changes included an intense inflammatory reaction at six weeks which had partially abated by 12 weeks. A proteoglycan-rich matrix at six weeks was partially replaced with collagen by 12 weeks. Similar changes were noted in the proximal cap which was acellular. Three patterns of microvessel formation were identified and defined based on the presence and extent of a "lead" neovessel. No major differences in pattern or extent of neovascularisation were noted between six and 12 weeks.CONCLUSIONS:Heterogeneity in neovascularisation patterns occurs during coronary CTO development in a porcine model. Non-invasive imaging to determine the predominant type of neovascularisation prior to and during CTO revascularisation may improve guidewire crossing success rates. This model may be useful for further exploration of CTO pathophysiology, and may aid in further refinements of in vivo imaging of CTO and development of novel therapeutic approaches to revascularisation of CTO, such as manipulations of the proximal cap, matrix composition, neovessel induction, and device testing.

Methods In nine pigs a CTO was created by percutaneously inserting a fibrin plug (AngiosealΤΜ) into the mid-todistal left anterior descending artery (LAD). Animals were studied six (n=3) or twelve weeks (n=6) later prior to sacrifice. An x-ray angiogram confirmed the LAD CTO at those time points. Cardiac MR (CMR) studies were then conducted on a 1.5T (n=6) or on a 3.0T MRI system (n=3), which included SSFP short axis sections for wall motion and post-gadolinium LGE-MRIs for viability. After sacrifice, both right and left coronary systems were injected with Microfil. X-ray or MSCT angiography of the fixed heart was obtained. A longitudinal cardiac section including the CTO lesion, proximal/distal LAD and the borders of infarction was removed and prepared in gel, then imaged in a microCT system at 27 micron resolution. LV functional parameters including wall thickness at end-systole (WTES) and end-diastole (WTED) were measured in border zone, infarct and remote region. Systolic wall thickening (SWT) was calculated using as (WTES-WTED) x100/ WTED. CMR and micro-CT data were processed using commercial software. The extent of collaterals on micro-CT images was rated qualitatively using a score from 0 to 3, indicating that no, minimal, moderate, or extensive collaterals were observed. A Student’s t-test was used for the statistical significance of differences between measurements at 6 and 12 weeks.

A multichannel optical coherence tomography (multi-beam OCT) system and an in vivo endoscopic imaging probe were developed using a swept-source OCT system. The distal optics were micro-machined to produce a high numerical aperture, multi-focus fibre optic array. This combination resulted in a transverse design resolution of <10 µm full width half maximum (FWHM) throughout the entire imaging range, while also increasing the signal intensity within the focus of the individual channels. The system was used in a pre-clinical rabbit study to acquire in vivo structural images of the colon and ex vivo images of the oesophagus and trachea. A good correlation between the structural multi-beam OCT images and H&E histology was achieved, demonstrating the feasibility of this high-resolution system and its potential for in vivo human endoscopic imaging.

Objective To demonstrate the feasibility of imaging human coronary atherosclerosis using a novel hybrid intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging catheter. Background IVUS and OCT have synergistic advantages and recent studies involving both modalities suggest the use of a hybrid imaging catheter may offer improved guidance of coronary interventions and plaque characterization. Methods A 1.3 m custom hybrid IVUS‐OCT imaging probe was built within a 4F catheter using a 42 MHz ultrasound transducer and an OCT imaging fiber. Coplanar images were simultaneously acquired ex vivo by both modalities in 31 arterial segments from 11 cadaveric human coronaries. IVUS and OCT images were acquired at 250 μm intervals, of which 13 of the arterial segments were selected as representative of a diverse set of pathological findings. The selected segments were then imaged with either digital X‐ray or micro‐CT, processed for histological analysis and compared with the corresponding IVUS and OCT images. Results Images of human coronary atherosclerosis using the hybrid IVUS‐OCT catheter demonstrated a range of vascular pathologies that were confirmed on histology. The anticipated synergistic advantages of each modality were qualitatively apparent, including the deeper tissue penetration of IVUS and the superior contrast, resolution and near‐field image quality of OCT. Conclusions Preliminary ex vivo images using a hybrid IVUS‐OCT catheter demonstrated feasibility in using the device for intracoronary imaging of atherosclerosis. Future studies will include in vivo imaging and larger samples sizes to enable quantitative comparisons of tissue characterization and feature identification using hybrid imaging catheters versus standalone IVUS and OCT imaging techniques. © 2012 Wiley Periodicals, Inc.

OBJECTIVES:The purpose of this study was to characterize the 3-dimensional structure of intravascular and extravascular microvessels during chronic total occlusion (CTO) maturation in a rabbit model. BACKGROUND:Intravascular microchannels are an important component of a CTO and may predict guidewire crossability. However, temporal changes in the structure and geographic localization of these microvessels are poorly understood. METHODS:A total of 39 occlusions were created in a rabbit femoral artery thrombin model. Animals were sacrificed at 2, 6, 12, and 24 weeks (n > or =8 occlusions per time point). The arteries were filled with a low viscosity radio-opaque polymer compound (Microfil) at 150 mm Hg pressure. Samples were scanned in a micro-computed tomography system to obtain high-resolution volumetric images. Analysis was performed in an image processing package that allowed for labeling of multiple materials. RESULTS:Two distinct types of microvessels were observed: circumferentially oriented "extravascular" and longitudinally oriented "intravascular" microvessels. Extravascular microvessels were evident along the entire CTO length and maximal at the 2-week time point. There was a gradual and progressive reduction in extravascular microvessels over time, with very minimal microvessels evident beyond 12 weeks. In contrast, intravascular microvessel formation was delayed, with peak vascular volume at 6 weeks, followed by modest reductions at later time points. Intravascular microvessel formation was more prominent in the body compared with that in the proximal and distal ends of the CTO. Sharply angulated connections between the intravascular and extravascular microvessels were present at all time points, but most prominent at 6 weeks. At later time points, the individual intravascular microvessels became finer and more tortuous, although the continuity of these microvessels remained constant beyond 2 weeks. CONCLUSIONS:Differences are present in the temporal and geographic patterns of intravascular and extravascular microvessel formation during CTO maturation.

We demonstrate the potential of a forward-looking Doppler optical coherence tomography (OCT) probe for color flow imaging in several commonly seen narrowed artery morphologies. As a proof of concept, we present imaging results of a surgically exposed thrombotic occlusion model that was imaged superficially to demonstrate that Doppler OCT can identify flow within the recanalization channels of a blocked artery. We present Doppler OCT images in which the flow is nearly antiparallel to the imaging direction. These images are acquired using a flexible 2.2-mm-diam catheter that used electrostatic actuation to scan up to 30 deg ahead of the distal end. Doppler OCT images of physiologically relevant flow phantoms consisting of small channels and tapered entrance geometries are demonstrated.

A time-dependent electrochemical and mechanical model of the bending of a conducting polymer actuator-driven structure is presented, and the predicted response is compared with experimental results. The model uses time constants obtained from a transmission line model to describe the electronic and ionic charge transport into the polymer actuator. It then relates the charge transport to the mechanical deflection of the actuator structure. The model is used to predict the time-dependent bending of an active catheter, which is ultimately intended for use in intravascular imaging. A commercial catheter is coated with polypyrrole and laser micromachined into electrodes, which are electrochemically activated, leading to bending of the catheter. The time-dependent bending is compared with the dynamic beam bending model, with measured physical properties including elastic moduli, strain to charge ratio, electronic conductivity, ionic conductivity and capacitance used in the model to successfully describe the dynamics. The results of this comparison are used to determine the primary factors limiting catheter bending speed, and to suggest an optimal polypyrrole geometry and electrochemical parameters in order to achieve faster response. (C) 2010 Society of Chemical Industry

In this paper conducting polymer based active catheters are presented. Design considerations along with the promise and challenges associated with conducting polymer driven devices are discussed. A conducting polymer driven intravascular catheter is described briefly and its design challenges such as structural rigidity and angle of bending are studied. Then a detailed description of a polypyrrole based active catheter that is ultimately intended for in-vivo imaging applications will be presented. The active catheter contains an optical fibre and is designed to scan the fibre in two dimensions at a speed of 30 Hz to provide real time imaging. The preliminary design was realized by fabricating polypyrrole actuators on a commercially available catheter and patterning the polymer using laser machining technique. The initial device was tested at lower speeds and an image was taken using optical coherence tomography (OCT). The primary challenge to achieving an effective polypyrrole driven catheter for real time imaging is to demonstrate high speed actuation with reasonable liftetime. According to our model, electrochemical characteristics of the conducting polymer such as electronic conductivity, ionic conductivity and electrochemical strain need to be improved to achieve the desired catheter scanning speed.

We report a high-power wavelength-swept laser source for multichannel optical coherence tomography (OCT) imaging. Wavelength tuning is performed by a compact telescope-less polygon-based filter in Littman arrangement. High output power is achieved by incorporating two serial semiconductor optical amplifiers in the laser cavity in Fourier domain mode-locked configuration. The measured wavelength tuning range of the laser is 111 nm centered at 1329 nm, coherence length of 5.5 mm, and total average output power of 131 mW at 43 kHz sweeping rate. Multichannel simultaneous OCT imaging at an equivalent A-scan rate of 258 kHz is demonstrated.

Minimally invasive surgical tools using catheter based technology plays an important role in biomedical diagnostics and treatments. Much research has focused on producing an actively controllable tip catheter to improve accuracy and efficiency over traditional passive catheters when navigating inside patients. In this work, we describe the design, fabrication and characterization of a novel laser-micromachined polypyrrole (PPy) based active catheter. Two-dimensional controlled bending motion of a four-electrode catheter is demonstrated. Combining such catheter with optical coherence tomography, which can provide subsurface visualization of biological tissue, imaging capability using the active catheter tip is also demonstrated.

We report a long coherence length, high power, and wide tuning range wavelength linearly swept fiber mode-locked laser based on polygon scanning filters. An output power of 52.6 mW with 112 nm wavelength tuning range at 62.6 kHz sweeping rate has been achieved. The coherence length is long enough to enable imaging over 8.1 mm depth when the sensitivity decreases by 8.7 dB (1/e(2)). The Fourier components are still distinguishable when the ranging depth exceeds 15 mm, which corresponds to 30 mm optical path difference in air. The parameters that are critical to OCT imaging quality such as polygon filter linewidth, the laser coherence length, output power, axial resolution and the Fourier sensitivity have been investigated theoretically and experimentally. Since the wavelength is swept linearly with time, an analytical approach has been developed for transforming the interference signal from equidistant spacing in wavelength to equidistant spacing in frequency. Axial resolution of 7.9 microm in air has been achieved experimentally that approaches the theoretical limit.

An active catheter intended for controllable intravascular maneuvers is presented and initial experimental results are shown. A commercial catheter is coated with polypyrrole and laser micromachined into electrodes, which are electrochemically activated, leading to bending of the catheter. The catheter's electro-chemo-mechanical properties are theoretically modeled to design the first prototype device, and used to predict an optimal polypyrrole thickness for the desired degree of bending within approximately 30 seconds. We compared the experimental result of catheter bending to the theoretical model with estimated electrochemical strain, showing reasonable agreement. Finally, we used the model to design an encapsulated catheter with polypyrrole actuation for improved intravascular compatibility and performance.

Chronic total occlusions (CTOs) are a subset of lesions that present a considerable burden to cardiovascular patients. There exists a strong clinical desire to improve non-surgical options for CTO revascularization. While several techniques, devices, and guide wires have been developed and refined for use in CTOs, the inability of angiography to adequately visualize occluded arterial segments makes interventions in this setting technically challenging. This review describes the current status of several invasive and non-invasive imaging techniques that may facilitate improved image guidance during CTO revascularization, with the goals of improving procedure safety and efficacy while reducing the time required to complete these interventions. Cardiac imaging also has important potential roles in selecting patients most likely to benefit from revascularization as well as pre-procedural planning, post-procedural assessment of revascularized segments and long-term outcomes studies. Modalities discussed include non-invasive techniques, such as CT(computed tomography) angiography and cardiac magnetic resonance imaging (MRI), as well as invasive techniques, such as intravascular ultrasound, optical coherence tomography, intravascular MRI, and conventional angiography. While some of these techniques have some evidence to support their use at present, others are at earlier stages of development. Strategies that combine imaging techniques with the use of interventional therapies may provide significant opportunities to improve results in CTO interventions and represent an active area of investigation.