Catheter-based Imaging Research Articles

Direct comparison of revascularization techniques in an adult North American moyamoya patient: case report and literature review

Abstract Objective To compare the effectiveness of two different revascularization techniques in a single patient with moyamoya disease. Setting Academic neurosurgery practice. Design Retrospective chart review and evaluation of radiographic results. Participants North American adult Caucasian female with moyamoya disease, who underwent direct revascularization in one hemisphere (superficial temporal artery–middle cerebral artery bypass) and indirect revascularization in the other hemisphere (pial synangiosis) in close temporal proximity. Outcome measures Clinical evaluation and radiographic follow-up for two years. Catheter-based cerebral angiography, CT angiography, and CT perfusion imaging were used to assess results. Results Both hemispheres showed revascularization following bypass with significant cortical supply. The direct bypass demonstrated superior flow and territory coverage. Conclusions This case provides a demonstration of both main revascularization techniques for moyamoya disease in a single adult patient over the same time period, allowing for a direct comparison. While the indirect technique showed evidence of revascularization, the direct bypass showed more vascular supply. A comprehensive review of recent case series supports this conclusion.

Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis.

The aim of this study was to validate novel imaging technology for simultaneous morphological and biochemical endogenous optical imaging of coronary atherosclerotic plaque. Optical coherence tomography (OCT) generates high-resolution 3D images of plaque morphology and endogenous fluorescence lifetime imaging microscopy (FLIM) characterizes biochemical composition. Both imaging modalities rely on plaque's intrinsic optical characteristics, making contrast agents unnecessary. A multimodal OCT/FLIM system was utilized to generate luminal biochemical maps superimposed on high-resolution (7 µm axial and 13 µm lateral) structural volumetric images. Forty-seven fresh postmortem human coronary segments were imaged: pathological intimal thickening (PIT, n = 26), fibroatheroma (FA, n = 12), thin-cap FA (TCFA, n = 2), and fibrocalcific plaque (CA, n = 7), determined by histopathology. Multimodal images were evaluated, and each plaque identified as PIT, FA, TCFA, or CA based on expert OCT readers, and as having high-lipid (HL), high-collagen (HC), or low-collagen/low-lipid (LCL) luminal composition based on linear discriminant analysis of FLIM. Of 47 plaques, 89.4% (42/47) of the plaques were correctly identified based on OCT/FLIM evaluation using tissue histopathology and immunohistochemistry as the gold standard. Four of the misclassifications corresponded to confusing PIT with HL luminal composition for FA with HL cap. The other corresponded to confusing FA with a HC cap for FA with an LCL cap. We have demonstrated the feasibility of accurate simultaneous OCT/FLIM morphological and biochemical characterization of coronary plaques at spatial resolutions and acquisition speeds compatible with catheter-based intravascular imaging. The success of this pilot study sets up future development of a multimodal intravascular imaging system that will enable studies that could help improve our understanding of plaque pathogenesis.

Multi-frequency intravascular ultrasound (IVUS) imaging.

Acute coronary syndrome (ACS) is frequently associated with the sudden rupture of a vulnerable atherosclerotic plaque within the coronary artery. Several unique physiological features, including a thin fibrous cap accompanied by a necrotic lipid core, are the targeted indicators for identifying the vulnerable plaques. Intravascular ultrasound (IVUS), a catheter-based imaging technology, has been routinely performed in clinics for more than 20 years to describe the morphology of the coronary artery and guide percutaneous coronary interventions. However, conventional IVUS cannot facilitate the risk assessment of ACS because of its intrinsic limitations, such as insufficient resolution. Renovation of the IVUS technology is essentially needed to overcome the limitations and enhance the coronary artery characterization. In this paper, a multi-frequency intravascular ultrasound (IVUS) imaging system was developed by incorporating a higher frequency IVUS transducer (80 to 150 MHz) with the conventional IVUS (30-50 MHz) system. The newly developed system maintains the advantage of deeply penetrating imaging with the conventional IVUS, while offering an improved higher resolution image with IVUS at a higher frequency. The prototyped multifrequency catheter has a clinically compatible size of 0.95 mm and a favorable capability of automated image co-registration. In vitro human coronary artery imaging has demonstrated the feasibility and superiority of the multi-frequency IVUS imaging system to deliver a more comprehensive visualization of the coronary artery. This ultrasonic-only intravascular imaging technique, based on a moderate refinement of the conventional IVUS system, is not only cost-effective from the perspective of manufacturing and clinical practice, but also holds the promise of future translation into clinical benefits.

Dynamic Assessment of the Endothelialization of Tissue-Engineered Blood Vessels Using an Optical Coherence Tomography Catheter-Based Fluorescence Imaging System.

Lumen endothelialization of bioengineered vascular scaffolds is essential to maintain small-diameter graft patency and prevent thrombosis postimplantation. Unfortunately, nondestructive imaging methods to visualize this dynamic process are lacking, thus slowing development and clinical translation of these potential tissue-engineering approaches. To meet this need, a fluorescence imaging system utilizing a commercial optical coherence tomography (OCT) catheter was designed to visualize graft endothelialization. C7 DragonFly™ intravascular OCT catheter was used as a channel for delivery and collection of excitation and emission spectra. Poly-dl-lactide (PDLLA) electrospun scaffolds were seeded with endothelial cells (ECs). Seeded cells were exposed to Calcein AM before imaging, causing the living cells to emit green fluorescence in response to blue laser. By positioning the catheter tip precisely over a specimen using high-fidelity electromechanical components, small regions of the specimen were excited selectively. The resulting fluorescence intensities were mapped on a two-dimensional digital grid to generate spatial distribution of fluorophores at single-cell-level resolution. Fluorescence imaging of endothelialization on glass and PDLLA scaffolds was performed using the OCT catheter-based imaging system as well as with a commercial fluorescence microscope. Cell coverage area was calculated for both image sets for quantitative comparison of imaging techniques. Tubular PDLLA scaffolds were maintained in a bioreactor on seeding with ECs, and endothelialization was monitored over 5 days using the OCT catheter-based imaging system. No significant difference was observed in images obtained using our imaging system to those acquired with the fluorescence microscope. Cell area coverage calculated using the images yielded similar values. Nondestructive imaging of endothelialization on tubular scaffolds showed cell proliferation with cell coverage area increasing from 15 ± 4% to 89 ± 6% over 5 days. In this study, we showed the capability of an OCT catheter-based imaging system to obtain single-cell resolution and to quantify endothelialization in tubular electrospun scaffolds. We also compared the resulting images with traditional microscopy, showing high fidelity in image capability. This imaging system, used in conjunction with OCT, could potentially be a powerful tool for in vitro optimization of scaffold cellularization, ensuring long-term graft patency postimplantation.

Correction of rotational distortion for catheter-based en face OCT and OCT angiography.

We demonstrate a computationally efficient method for correcting the nonuniform rotational distortion (NURD) in catheter-based imaging systems to improve endoscopic en face optical coherence tomography (OCT) and OCT angiography. The method performs nonrigid registration using fiducial markers on the catheter to correct rotational speed variations. Algorithm performance is investigated with an ultrahigh-speed endoscopic OCT system and micromotor catheter. Scan nonuniformity is quantitatively characterized, and artifacts from rotational speed variations are significantly reduced. Furthermore, we present endoscopic en face OCT and OCT angiography images of human gastrointestinal tract in vivo to demonstrate the image quality improvement using the correction algorithm.

Fiber-optic system for dual-modality imaging of glucose probes 18F-FDG and 6-NBDG in atherosclerotic plaques.

BackgroundAtherosclerosis is a progressive inflammatory condition that underlies coronary artery disease (CAD)–the leading cause of death in the United States. Thus, the ultimate goal of this research is to advance our understanding of human CAD by improving the characterization of metabolically active vulnerable plaques within the coronary arteries using a novel catheter-based imaging system. The aims of this study include (1) developing a novel fiber-optic imaging system with a scintillator to detect both 18F and fluorescent glucose probes, and (2) validating the system on ex vivo murine plaques.MethodsA novel design implements a flexible fiber-optic catheter consisting of both a radio-luminescence and a fluorescence imaging system to detect radionuclide 18F-fluorodeoxyglucose (18F-FDG) and the fluorescent analog 6-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-6-Deoxyglucose (6-NBDG), respectively. Murine macrophage-rich atherosclerotic carotid plaques were imaged ex vivo after intravenous delivery of 18F-FDG or 6-NBDG. Confirmatory optical imaging by IVIS-200 and autoradiography were also performed.ResultsOur fiber-optic imaging system successfully visualized both 18F-FDG and 6-NBDG probes in atherosclerotic plaques. For 18F-FDG, the ligated left carotid arteries (LCs) exhibited 4.9-fold higher radioluminescence signal intensity compared to the non-ligated right carotid arteries (RCs) (2.6×104±1.4×103 vs. 5.4×103±1.3×103 A.U., P = 0.008). Similarly, for 6-NBDG, the ligated LCs emitted 4.3-fold brighter fluorescent signals than the control RCs (1.6×102±2.7×101 vs. 3.8×101±5.9 A.U., P = 0.002). The higher uptake of both 18F-FDG and 6-NBDG in ligated LCs were confirmed with the IVIS-200 system. Autoradiography further verified the higher uptake of 18F-FDG by the LCs.ConclusionsThis novel fiber-optic imaging system was sensitive to both radionuclide and fluorescent glucose probes taken up by murine atherosclerotic plaques. In addition, 6-NBDG is a promising novel fluorescent probe for detecting macrophage-rich atherosclerotic plaques.

Diagnostic fiber-based optical imaging catheters

Fiber optics miniaturization and advances in signal acquisition and processing have allowed the development of fiber-based optical imaging catheters that permit instantaneous luminal organ imaging. This technique is applicable in clinical settings for diagnosing various diseases. Intravascular optical coherence tomography (IV-OCT), a catheter-based optical imaging technique, acquires high-resolution cross-sectional human coronary arterial wall imaging, enabling precise assessment of coronary atherosclerosis. OCT with a ballooncentering catheter or a tethered capsule acquires comprehensive three-dimensional images of the distal esophagus for diagnostic imaging in patients with esophageal diseases, including Barrett’s esophagus. Spectrally encoded confocal microscopy (SECM), an advanced type of confocal microscopy that uses diffraction grating and a broadband laser source to laterally scan the sample without mechanical motion, has been developed as a tethered confocal endomicroscopy capsule to diagnose and monitor eosinophilic esophagitis, an allergic condition in the esophageal wall. In this review, the authors describe the recent development of fiber-based imaging catheters with rotary scanning for diagnosing various diseases in luminal organs, including the coronary artery and esophagus. Further developments, including miniaturization of optics, increased speed, and multimodal acquisition, could significantly improve diagnostic capability to improve patient care.

Molecular intravascular imaging approaches for atherosclerosis.

Coronary artery disease (CAD) is an inflammatory process that results in buildup of atherosclerosis, typically lipid-rich plaque in the arterial wall. Progressive narrowing of the vessel wall and subsequent plaque rupture can lead to myocardial infarction and death. Recent advances in intravascular fluorescence imaging techniques have provided exciting coronary artery-targeted platforms to further characterize the molecular changes that occur within the vascular wall as a result of atherosclerosis and following coronary stent-induced vascular injury. This review will summarize exciting recent developments in catheter-based imaging of coronary arterial-sized vessels; focusing on two-dimensional near-infrared fluorescence imaging (NIRF) molecular imaging technology as an approach to specifically identify inflammation and fibrin directly within coronary artery-sized vessels. Intravascular NIRF is anticipated to provide new insights into the in vivo biology underlying high-risk plaques, as well as high-risks stents prone to stent restenosis or stent thrombosis.

In-vivo segmentation and quantification of coronary lesions by optical coherence tomography images for a lesion type definition and stenosis grading.

Optical coherence tomography (OCT) is a catheter-based medical imaging technique that produces cross-sectional images of blood vessels. This technique is particularly useful for studying coronary atherosclerosis. In this paper, we present a new framework that allows a segmentation and quantification of OCT images of coronary arteries to define the plaque type and stenosis grading. These analyses are usually carried out on-line on the OCT-workstation where measuring is mainly operator-dependent and mouse-based. The aim of this program is to simplify and improve the processing of OCT images for morphometric investigations and to present a fast procedure to obtain 3D geometrical models that can also be used for external purposes such as for finite element simulations. The main phases of our toolbox are the lumen segmentation and the identification of the main tissues in the artery wall. We validated the proposed method with identification and segmentation manually performed by expert OCT readers. The method was evaluated on ten datasets from clinical routine and the validation was performed on 210 images randomly extracted from the pullbacks. Our results show that automated segmentation of the vessel and of the tissue components are possible off-line with a precision that is comparable to manual segmentation for the tissue component and to the proprietary-OCT-console for the lumen segmentation. Several OCT sections have been processed to provide clinical outcome.

TU-F-12A-06: BEST IN PHYSICS (IMAGING) - A Novel Catheter-Based Radionuclide Imaging System to Characterize Atherosclerotic Plaque

Purpose: Atherosclerosis underlies coronary artery diseases, the leading cause of death in the United States and worldwide. In this study, we developed a novel catheter-based radionuclide imaging (CRI) system to image 18F-fluorodeoxyglucose (18F-FDG), a radionuclide, a marker of vascular inflammation, in murine carotid arteries and characterized the system for spatial resolution from multiple scintillating materials. Methods: The catheter system includes 35 mm and 8 mm fixed focal length lenses, which are subsequently connected to a CMOS camera and fiber holder. The distal ferrule of an image bundle is terminated with a wide-angle lens. The novelty of this system is a scintillating balloon with a crystal tip in the front of the wide angle lens to image light from the decay of 18F-FDG emission signal. The scintillating balloon is fabricated from 1mL of silicone RTV catalyst mixed with 1 mL base and 50 mg/mL calcium fluoride doped with Europium (CaF2:Eu). To identify the optimal scintillating materials with respect to resolution, we calculated modulation transfer function (MTF) of Yttrium Aluminum Garnet doped with Cerium (YAG:Ce), anthracene, and CaF2:Eu phosphors using a thin line optical phantom (Fig. 1a-1b). Macrophage-rich FVB murine atherosclerotic carotid plaque model (n = 4) was used in ex vivo experiments. Confirmatory imaging was also performed by an external optical imaging system (IVIS-200). Results: Analysis of the different phosphors (Fig 1b) showed that CaF2:Eu enabled the best resolution of 1.2μm. The CRI system visualized 18F-FDG in atherosclerotic plaques (Fig. 1d). The ligated left carotid (LR) artery exhibited 4× higher 18F-FDG signal intensity compared to the non-ligated right carotid (negative control) artery (1.65×10^2 ±4.07×10^1 vs. 4.44×10^1±2.17×10^0, A.U., p = 0.005) and confirmed with IVIS-200 (Fig. 1d). Conclusion: This CRI system enables high-resolution and sensitive detection of 18F-FDG uptake by murine atherosclerotic plaques.

Mapping Intravascular Ultrasound Controversies in Interventional Cardiology Practice

Intravascular ultrasound is a catheter-based imaging modality that was developed to investigate the condition of coronary arteries and assess the vulnerability of coronary atherosclerotic plaques in particular. Since its introduction in the clinic 20 years ago, use of intravascular ultrasound innovation has been relatively limited. Intravascular ultrasound remains a niche technology; its clinical practice did not vastly expand, except in Japan, where intravascular ultrasound is an appraised tool for guiding percutaneous coronary interventions. In this qualitative research study, we follow scholarship on the sociology of innovation in exploring both the current adoption practices and perspectives on the future of intravascular ultrasound. We conducted a survey of biomedical experts with experience in the technology, the practice, and the commercialization of intravascular ultrasound. The collected information enabled us to map intravascular ultrasound controversies as well as to outline the dynamics of the international network of experts that generates intravascular ultrasound innovations and uses intravascular ultrasound technologies. While the technology is praised for its capacity to measure coronary atherosclerotic plaque morphology and is steadily used in clinical research, the lack of demonstrated benefits of intravascular ultrasound guided coronary interventions emerges as the strongest factor that prevents its expansion. Furthermore, most of the controversies identified were external to intravascular ultrasound technology itself, meaning that decision making at the industrial, financial and regulatory levels are likely to determine the future of intravascular ultrasound. In light of opinions from the responding experts', a wider adoption of intravascular ultrasound as a stand-alone imaging modality seems rather uncertain, but the appeal for this technology may be renewed by improving image quality and through combination with complementary imaging modalities.

Abstract 313: A Novel Catheter-Based Radionuclide Imaging System to Characterize Atherosclerotic Plaque

Objectives: Atherosclerosis underlies coronary artery diseases—the leading cause of death in the United States and worldwide. In this study, we developed a novel catheter-based radionuclide imaging (CRI) system to image 18 F-fluorodeoxyglucose ( 18 F-FDG), a radionuclide, a marker of vascular inflammation, in murine carotid arteries and characterized the system for spatial resolution from multiple scintillating materials. Methods: The catheter system includes 35 mm and 8 mm fixed focal length lenses, which are subsequently connected to a CMOS camera and fiber holder. The distal ferrule of an image bundle is terminated with a wide-angle lens. The novelty of this system is a scintillating balloon with a crystal tip in the front of the wide angle lens to image light from the decay of 18 F-FDG emission signal. The scintillating balloon is fabricated from 1mL of silicone RTV catalyst mixed with 1 mL base and 50 mg/mL calcium fluoride doped with Europium (CaF 2 :Eu). To identify the optimal scintillating materials with respect to resolution, we calculated modulation transfer function (MTF) of Yttrium Aluminum Garnet doped with Cerium (YAG:Ce), anthracene, and CaF 2 :Eu phosphors using a thin line optical phantom (Fig. 1a-1b). Macrophage-rich FVB murine atherosclerotic carotid plaque model (n = 4) was used in ex vivo experiments. Confirmatory imaging was also performed by an external optical imaging system (IVIS-200). Results: Analysis of the different phosphors (Fig 1b) showed that CaF 2 :Eu enabled the best resolution of 1.2μm. The CRI system visualized 18 F-FDG in atherosclerotic plaques (Fig. 1d). The ligated left carotid (LR) artery exhibited 4.9х higher 18 F-FDG signal intensity compared to the non-ligated right carotid (negative control) artery (2.6х10 4 ±1.4х10 3 vs. 5.4х10 3 ±1.3х10 3 , A.U., p = 0.008) and confirmed with IVIS-200 (Fig. 1d). Conclusions: This CRI system enables high-resolution and sensitive detection of 18 F-FDG uptake by murine atherosclerotic plaques.

Assessment of coronary atherosclerosis using optical coherence tomography.

Optical coherence tomography (OCT) is a catheter-based imaging system that uses near-infrared light to produce cross-sectional images of the coronary arteries. With its extraordinarily high resolution (10-20 μm), OCT allows clinicians to observe various morphological features of coronary atherosclerosis in vivo. For example, intimal thickening presents as homogeneous, signal-rich regions on OCT, while fibroatheroma with a lipid-rich necrotic core is characterized by the presence of signal-poor regions with a diffuse border. Furthermore, plaque rupture is detected in 50〜70% of culprit lesions of acute coronary syndrome (ACS), and plaque erosion develops over areas of intimal thickening and/or thick-cap fibroatheroma. Meanwhile, calcified nodules are common in older patients with hypertension and chronic renal disease. Platelet-rich thrombi are visualized as low backscattering structures and often detected in patients with unstable angina, whereas red blood cell-rich thrombi exhibit a high backscattering structure with signal-free shadowing and are frequently noted in patients with acute myocardial infarction. Moreover, OCT-derived thin cap fibroatheroma has been shown to be a predictor of subsequent plaque progression and acute coronary events, while vasa vasorum and the macrophage density are associated with a thin fibrous cap and large necrotic core as well as increased serum levels of inflammatory biomarkers. One current challenge of OCT examinations is to detect morphologic characteristics capable of discriminating vulnerable from stable plaques. The ability to detect vulnerable plaques in vivo would allow physicians to identify patients at high risk for adverse coronary events, thus significantly helping to prevent ACS.

Evaluating the feasibility of acoustic radiation force impulse shear wave elasticity imaging of the uterine cervix with an intracavity array: a simulation study

The uterine cervix softens, shortens, and dilates throughout pregnancy in response to progressive disorganization of its layered collagen microstructure. This process is an essential part of normal pregnancy, but premature changes are associated with preterm birth. Clinically, there are no reliable noninvasive methods to objectively measure cervical softening or assess cervical microstructure. The goal of these preliminary studies was to evaluate the feasibility of using an intracavity ultrasound array to generate acoustic radiation force impulse (ARFI) excitations in the uterine cervix through simulation, and to optimize the acoustic radiation force (ARF) excitation for shear wave elasticity imaging (SWEI) of the tissue stiffness. The cervix is a unique soft tissue target for SWEI because it has significantly greater acoustic attenuation (α = 1.3 to 2.0 dB·cm(-1)·MHz(-)1) than other soft tissues, and the pathology being studied tends to lead to an increase in tissue compliance, with healthy cervix being relatively stiff compared with other soft tissues (E ≈ 25 kPa). Additionally, the cervix can only be accessed in vivo using a transvaginal or catheter-based array, which places additional constraints on the excitation focal characteristics that can be used during SWEI. Finite element method (FEM) models of SWEI show that larger-aperture, catheter-based arrays can utilize excitation frequencies up to 7 MHz to generate adequate focal gain up to focal depths 10 to 15 mm deep, with higher frequencies suffering from excessive amounts of near-field acoustic attenuation. Using full-aperture excitations can yield ~40% increases in ARFI-induced displacements, but also restricts the depth of field of the excitation to ~0.5 mm, compared with 2 to 6 mm, which limits the range that can be used for shear wave characterization of the tissue. The center-frequency content of the shear wave particle velocity profiles ranges from 1.5 to 2.5 kHz, depending on the focal configuration and the stiffness of the material being imaged. Overall, SWEI is possible using catheter-based imaging arrays to generate adequate displacements in cervical tissue for shear wave imaging, although specific considerations must be made when optimizing these arrays for this shear wave imaging application.

Spectral binning for mitigation of polarization mode dispersion artifacts in catheter-based optical frequency domain imaging

Polarization mode dispersion (PMD) has been recognized as a significant barrier to sensitive and reproducible birefringence measurements with fiber-based, polarization-sensitive optical coherence tomography systems. Here, we present a signal processing strategy that reconstructs the local retardation robustly in the presence of system PMD. The algorithm uses a spectral binning approach to limit the detrimental impact of system PMD and benefits from the final averaging of the PMD-corrected retardation vectors of the spectral bins. The algorithm was validated with numerical simulations and experimental measurements of a rubber phantom. When applied to the imaging of human cadaveric coronary arteries, the algorithm was found to yield a substantial improvement in the reconstructed birefringence maps.

Imaging and characterization of bioengineered blood vessels within a bioreactor using free‐space and catheter‐based OCT

Regenerative medicine involves the bioengineering of a functional tissue or organ by seeding living cells on a biodegradable scaffold cultured in a bioreactor. A major barrier to creating functional tissues, however, has been the inability to monitor the dynamic and complex process of scaffold maturation in real time, making control and optimization extremely difficult. Current methods to assess maturation of bioengineered constructs, such as histology or organ bath physiology, are sample-destructive. Optical coherence tomography (OCT) has recently emerged as a key modality for structural assessment of native blood vessels as well as engineered vessel mimics. The objective of this study was to monitor and assess in real time the development of a bioengineered blood vessel using a novel approach of combining both free-space and catheter-based OCT imaging in a new quartz-walled bioreactor. Development of the blood vessel was characterized by changes in thickness and scattering coefficient over a 30-day period. We constructed a novel blood vessel bioreactor utilizing a rotating cylindrical quartz cuvette permitting free-space OCT imaging of an installed vessel's outer surface. A vascular endoscopic OCT catheter was used to image the lumen of the vessels. The quartz cuvette permits 360 degree, free-space OCT imaging of the blood vessel. Bioengineered blood vessels were fabricated using biodegradable polymers (15% PCL/collagen, ∼300 µm thick) and seeded with CH3 10t1/2 mesenchymal stem cells. A swept-source OCT imaging system comprised of a 20 kHz tunable laser (Santec HSL2000) with 1,300 nm central wavelength and 110 nm FWHM bandwidth was used to assess the vessels. OCT images were obtained at days 1, 4, 7, 14, 21, and 30. Free-space (exterior surface) OCT images were co-registered with endoscopic OCT images to determine the vessel wall thickness. DAPI-stained histological sections, acquired at same time point, were evaluated to quantify wall thickness and cellular infiltration. Non-linear curve fitting of free-space OCT data to the extended Huygen-Fresnel model was performed to determine optical scattering properties. Vessel wall thickness increased from 435 ± 15 µm to 610 ± 27 µm and Vessel scattering coefficient increased from 3.73 ± 0.32 cm⁻¹ to 5.74 ± 0.06 cm⁻¹ over 30 days. Histological studies showed cell migration from the scaffold surface toward the lumen and cell proliferation over the same time course. The imaging procedure did not have any significant impact on scaffold dimensions, cell migration, or cell proliferation. This study suggests that combination of free-space and catheter-based OCT for blood vessel imaging provides accurate structural information of the developing blood vessel. We determined that free-space OCT images could be co-registered with catheter-based OCT images to monitor structural features such as wall thickness or delamination of the developing tissue-engineered blood vessel within a bioreactor. Structural parameters and optical properties obtained from OCT imaging correlate with histological sections of the blood vessel and could potentially be used as markers to non-invasively and non-destructively assess regeneration of engineered tissues in real time.

YIA1: IMAGING BEYOND THE LUMEN: NEAR INFRA-RED IN VIVO MOLECULAR IDENTIFICATION OF OXIDISED LDL IN ATHEROSCLEROSIS USING MAB LO1, AND THE GENERATION AND DEVELOPMENT OF ITS MOLECULARLY EXPRESSED CYSTEINE-TAGGED CHIMERIC FAB CONSTRUCT (LO1-FAB-CYS)

<h3>Introduction</h3> The <i>in vivo</i> identification of vulnerable atherosclerotic plaque remains elusive despite current advances in intravascular morphological imaging technologies such as IVUS-VH and OCT. With the recent advent of intra-vascular catheter-based optical fluorescence domain imaging combined with near infra-red fluorescence (OFDI-NIRF), we aim to translationally develop a novel NIRF antibody-based technique for the identification of oxidised LDL in atherosclerosis. <h3>Methods and Results</h3> We isolated a previously unknown IgG3κ autoantibody against oxLDL (designated LO1) from an LDL receptor deficient hypercholesterolaemic mouse. Characterisation of LO1 revealed specificity for malondialdehyde-conjugated LDL (MDA-LDL), an epitope expressed in oxidised LDL and which is known to reflect vulnerability in human atherosclerotic lesions. Immunohistochemical (IHC) staining of biotinylated LO1 showed binding to advanced mouse atherosclerotic plaque and to necrotic core within culprit human carotid atherosclerotic plaque. We used the immunoglobulin SH groups to successfully label LO1 with a Near Infra-Red Fluorescence (NIRF) reporter VivoTag-S MAL 750 (designated LO1-750) for in vivo imaging studies. Using two optical imaging techniques (IVIS Spectrum combined with hybrid high resolution CT; Fluorescence Molecular Tomography (FMT)) we have demonstrated that intra-venously injected LO1-750 sensitively and specifically identifies atherosclerotic lesions <i>in vivo</i> in the aortae of LDLr^−/− mouse model (Figure&nbsp;1) but not in control mice. LO1-750 also demonstrated superior specificity for lesional regions of interest (ROIs) than a caged MMP probe. <i>In situ en face</i> IHC on extracted aortae with LO1-750 showed localisation to the aortic arch and root, with co localisation to the sub-endothelium as demonstrated by counter injection with an anti CD-31 antibody (Figure&nbsp;2). In order to facilitate future use in human subjects, LO1 was successfully sequenced and sequence verified as germline. It was then expressed in HEK cells as a chimeric Fab (∼50kD), with murine VH and VL and human CH1 and CL. The terminus of CH1 extends to the THTC of the hinge region to provide the free cysteine for NIRF labelling<i>. In vitro</i> characterisation of the construct revealed maintained function when purified over an anti-human CH1 column and labelled with Vivo Tag-S MAL 750. Injected LO1-cys-fab localised to the sub-endothelium of the diseased aortic arch of LDLr^−/− mice in a similar fashion to the native LO1 antibody. Initial FMT studies have confirmed localisation to atherosclerotic lesions within the LDLr^−/− model. <h3>Conclusion</h3> The in vivo optical imaging of oxidised LDL is possible with LO1 and the chimerically humanised LO1-Cys-Fab. Future work will aim to translate this to optical imaging of atherosclerosis in humans.

Haemodynamics and catheter-based imaging in the diagnosis of venous disease. An interventional targeted approach

The investigation of patients with severe chronic venous insufficiency (CVI, C3-C6) represents a challenge that requires the understanding of venous pathophysiology and a multidisciplinary approach; it should be aimed to assess valve function, evaluate the haemodynamic significance of obstruction and assess the function of the vein-muscle pump. Combining haemodynamic tests and imaging techniques best accomplish the investigation of these three aspects of the pathophysiology in CVI. The information obtained from ambulatory venous pressure and color duplex ultrasound is accurate when assessing reflux in the different segments of the different venous systems. The valve anatomic location and dynamic picture is supplied by descending phlebography. In case of venous obstruction, the haemodynamic tests lack accuracy and sensitivity. Therefore, imaging catheter techniques have to fill-in to depict vein morphology as well as inflow/outflow characteristics. The participation of several specialties in the investigation of these patients widens the treatment possibilities by identifying those who may benefit from advanced surgical and/or endovascular procedures. This interventional-targeted approach should be a centralized function.

Segmentation of the luminal border in intravascular ultrasound B-mode images using a probabilistic approach

Intravascular ultrasound (IVUS) is a catheter-based medical imaging technique that produces cross-sectional images of blood vessels and is particularly useful for studying atherosclerosis. In this paper, we present a computational method for the delineation of the luminal border in IVUS B-mode images. The method is based in the minimization of a probabilistic cost function (that deforms a parametric curve) which defines a probability field that is regularized with respect to the given likelihoods of the pixels belonging to blood and non-blood. These likelihoods are obtained by a Support Vector Machine classifier trained using samples of the lumen and non-lumen regions provided by the user in the first frame of the sequence to be segmented. In addition, an optimization strategy is introduced in which the direction of the steepest descent and Broyden-Fletcher-Goldfarb-Shanno optimization methods are linearly combined to improve convergence. Our proposed method (MRK) is capable of segmenting IVUS B-mode images from different systems and transducer frequencies without the need of any parameter tuning, and it is robust with respect to changes of the B-mode reconstruction parameters which are subjectively adjusted by the interventionist. We validated the proposed method on six 20MHz and six 40MHz IVUS stationary sequences corresponding to regions with different degrees of stenosis, and evaluated its performance by comparing the segmentation results with manual segmentation by two observers. Furthermore, we compared our method with the segmentation results on the same sequences as provided by the authors of three other segmentation methods available in the literature. The performance of all methods was quantified using Dice and Jaccard similarity indexes, Hausdorff distance, linear regression and Bland-Altman analysis. The results indicate the advantages of our method for the segmentation of the lumen contour.

New Frontiers in the Feasibility of Optical Coherence Tomography in Carotid Arteries

Optical coherence tomography (OCT) is a catheter-based invasive intravascular imaging system that provides unprecedented microstructural information on atherosclerotic plaques. Multiple research teams have begun to explore the use of OCT imaging for carotid plaque assessment (with both occlusive[1][