J. Jacob Mancuso

Detection of macrophages in atherosclerotic tissue using magnetic nanoparticles and differential phase optical coherence tomography

We demonstrate the detection of iron oxide nanoparticles taken up by macrophages in atherosclerotic plaque with differential phase optical coherence tomography (DP-OCT). Magneto mechanical detection of nanoparticles is demonstrated in hyperlipidemic Watanabe and balloon-injured fat-fed New Zealand white rabbits injected with monocrystalline iron oxide nanoparticles (MIONs) of < 40 nm diam. MIONs taken up by macrophages was excited by an oscillating magnetic flux density and resulting nanometer tissue surface displacement was detected by DP-OCT. Frequency response of tissue surface displacement in response to an externally applied magnetic flux density was twice the stimulus frequency as expected from the equations of motion for the nanoparticle cluster.

Combined two-photon luminescence microscopy and OCT for macrophage detection in the hypercholesterolemic rabbit aorta using plasmonic gold nanorose

The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two‐channel two‐photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta‐based macrophages using plasmonic gold nanorose as an imaging contrast agent.

Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles

The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P<0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P<0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques.

Use of near-infrared luminescent gold nanoclusters for detection of macrophages

We determined the effect of aggregation and coating thickness of gold on the luminescence of nanoparticles engulfed by macrophages and in gelatin phantoms. Thin gold-coated iron oxide nanoclusters (nanoroses) have been developed to target macrophages to provide contrast enhancement for near-infrared optical imaging applications. We compare the brightness of nanoroses luminescent emissions in response to 635 nm laser excitation to other nanoparticles including nanoshells, nanorods, and Cy5 conjugated iron oxide nanoparticles. Luminescent properties of all these nanoparticles were investigated in monomeric and aggregated form in gelatin phantoms and primary macrophage cell cultures using confocal microscopy. Aggregation of the gold nanoparticles increased luminescence emission and correlated with increased surface mass of gold per nanoparticle (nanoshells 37 ± 14.30 × 10(-3) brightness with 1.23 × 10(-4) wt of gold (g)/nanoparticle versus original nanorose 1.45 ± 0.37 × 10(-3) with 2.10 × 10(-16) wt of gold/nanoparticle, p<0.05). Nanoshells showed greater luminescent intensity than original nanoroses or Cy5 conjugated iron oxide nanoparticles when compared as nanoparticles per macrophage (38 ± 10 versus 11 ± 2.8 versus 17 ± 6.5, p<0.05, respectively, ANOVA), but showed relatively poor macrophage uptake (1025 ± 128 versus 7549 ± 236 versus 96,000 nanoparticles/cell, p<0.05, student t-test nanoshells versus nanoroses). Enhancement of gold fluorescent emissions by nanoparticles can be achieved by reducing the thickness of the gold coating, by clustering the gold on the surface of the nanoparticles (nanoshells), and by clustering the gold nanoparticles themselves.

Sunflower artifact in OCT.

The sunflower effect is an intravascular optical coherence tomography (IV-OCT) artifact observed when imaging metal coronary stents deployed in patients during cardiac catheterization and appears as a bending of stent struts toward the imaging catheter—analogous to a sunflower bending toward the

Intravascular optical coherence tomography light scattering artifacts: merry-go-rounding, blooming, and ghost struts

Abstract. We sought to elucidate the mechanisms underlying two common intravascular optical coherence tomography (IV-OCT) artifacts that occur when imaging metallic stents: “merry-go-rounding” (MGR), which is an increase in strut arc length (SAL), and “blooming,” which is an increase in the strut reflection thickness (blooming thickness). Due to uncontrollable variables that occur in vivo, we performed an in vitro assessment of MGR and blooming in stented vessel phantoms. Using Xience V and Driver stents, we examined the effects of catheter offset, intimal strut coverage, and residual blood on SAL and blooming thickness in IV-OCT images. Catheter offset and strut coverage both caused minor MGR, while the greatest MGR effect resulted from light scattering by residual blood in the vessel lumen, with 1% hematocrit (Hct) causing a more than fourfold increase in SAL compared with saline (p<0.001). Residual blood also resulted in blooming, with blooming thickness more than doubling when imaged in 0.5% Hct compared with saline (p<0.001). We demonstrate that a previously undescribed mechanism, light scattering by residual blood in the imaging field, is the predominant cause of MGR. Light scattering also results in blooming, and a newly described artifact, three-dimensional-MGR, which results in “ghost struts” in B-scans.

Intravascular OCT Imaging Artifacts

This chapter discusses many intravascular imaging artifacts that may be encountered when interpreting OCT images from coronary arteries in the clinic or in research settings. All OCT artifacts originate in either the propagation of light in the vessel lumen, signal acquisition or polar-to-rectangular conversion. When these artifacts are recognized and understood, OCT image interpretation can become much more accurate.

Optical coherence tomography: shining the light on peripheral intervention.

Stefano et al. present a case of superficial femoral artery intervention complicated by spiral dissection [1]. Traditionally, nonflow limiting dissections have been managed conservatively in coronary and even more so in peripheral lower extremity interventions. However, the use of intravascular imaging facilitates the management plan [2]. In addition to intravascular ultrasound (IVUS), the availability of optical coherence tomography (OCT) has provided an additional tool for the assessment of suspected dissections. As the authors state, the approval of second generation FD-OCT systems have allowed clinicians to rapidly obtain high resolution intravascular images over long arterial segments without the cumbersome balloon occlusion required of the time-domain OCT. Their presentation of OCT imaging as an adjunct to management of dissection in femoropopliteal intervention is fairly novel and their high quality images free of blood artifact demonstrate how far OCT has come in the recent past. Clinicians interested in using OCT in peripheral arteries, however, must be mindful of the differences and limitations of this technology compared to intravascular ultrasound. The foremost limitation of OCT is decreased tissue penetrance at the expense of its high resolution. Intraluminal blood clearance is vital to obtaining high quality images and thus, high grade flow limiting stenoses can affect the ability to clear the vessel lumen. Higher injection rates (and thus higher volume) of flush medium are required for adequate blood clearance compared to coronary imaging. In the US, the St. Jude Medical C7XR (St. Jude, St. Paul, MN) is approved for imaging with contrast injections, which we have to be cognizant of in patients with renal insufficiency. Saline or 50% contrast mixtures can be used; however, the vessel caliber interpretation may be inaccurate due to the different indices of refraction compared to 100% contrast for which the system is calibrated. Peripheral chronic total occlusion (CTO) interventions also present challenges for OCT when faced with a subintimal wire position and intraluminal flush medium is not present. Recent approval of an OCT equipped atherectomy catheter, which is specifically designed to image CTOs while performing atherectomy across the occlusion is another step forward.