Roman V. Kuranov

Depth-resolved blood oxygen saturation measurement by dual-wavelength photothermal (DWP) optical coherence tomography

Non-invasive depth-resolved measurement of hemoglobin oxygen saturation (SaO2) levels in discrete blood vessels may have implications for diagnosis and treatment of various pathologies. We introduce a novel Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) for non-invasive depth-resolved measurement of SaO2 levels in a blood vessel phantom. DWP OCT SaO2 is linearly correlated with blood-gas SaO2 measurements. We demonstrate 6.3% precision in SaO2 levels measured a phantom blood vessel using DWP-OCT with 800 and 765 nm excitation wavelengths. Sources of uncertainty in SaO2 levels measured with DWP-OCT are identified and characterized.

Depth resolved photothermal OCT detection of macrophages in tissue using nanorose

Application of photothermal Optical Coherence Tomography (OCT) to detect macrophages in ex vivo rabbit arteries which have engulfed nanoclusters of gold coated iron oxide (nanorose) is reported. Nanorose engulfed by macrophages associated with atherosclerotic lesions in rabbit arteries absorb incident laser (800nm) energy and cause optical pathlength (OP) variation which is measured using photothermal OCT. OP variation in polydimethyl siloxane tissue phantoms containing varying concentrations of nanorose match values predicted from nanoparticle and material properties. Measurement of OP variation in rabbit arteries in response to laser excitation provides an estimate of nanorose concentration in atherosclerotic lesions of 2.5x109 particles/ml. OP variation in atherosclerotic lesions containing macrophages taking up nanorose has a different magnitude and profile from that observed in control thoracic aorta without macrophages and is consistent with macrophage presence as identified with RAM-11 histology staining. Our results suggest that tissue regions with macrophages taking up nanorose can be detected using photothermal OCT.

Effects of Magnetic Field on the Motion of Multiphase Fluids Containing Paramagnetic Nanoparticles in Porous Media

When paramagnetic nanoparticles are adsorbed at the oil-water interface or dispersed in one of the fluid phases in reservoir rock pores, then exposed to an external magnetic field, the resultant particle movements displace the interface. Interfacial tension acts as a restoring force, leading to interfacial fluctuation and a pressure (sound) wave. Here we focus on the interface motion. We apply the theory of ferrofluids to the case of an interface in a cylindrical pore. The predictions are consistent with experiments with an aqueous suspension of iron oxide nanorods in which the interface motion is measured by optical coherence tomography. The relative densities of the fluid phases (air/aqueous and dodecane/aqueous in our case) strongly affect the displacement of the interface. Application of a magnetic field introduces pressure-like terms into the equation of fluid phase motion. We then recast the problem in terms of interface motion, extending a numerical interface-tracking model based on the level-set method to account for capillarity and magnetic pressures simultaneously. We use the model to illustrate the motion of an interface between inviscid fluids at the pore scale when magnetic forces are imposed on one fluid phase.

Lamina-Specific Anatomic Magnetic Resonance Imaging of the Human Retina

PURPOSEnMagnetic resonance imaging (MRI) of the human retina faces two major challenges: eye movement and hardware limitation that could preclude human retinal MRI with adequate spatiotemporal resolution. This study investigated eye-fixation stability and high-resolution anatomic MRI of the human retina on a 3-Tesla (T) MRI scanner. Comparison was made with optical coherence tomography (OCT) on the same subjects.nnnMETHODSnEye-fixation stability of protocols used in MRI was evaluated on four normal volunteers using an eye tracker. High-resolution MRI (100 × 200 × 2000 μm) protocol was developed on a 3-T scanner. Subjects were instructed to maintain stable eye fixation on a target with cued blinks every 8 seconds during MRI. OCT imaging of the retina was performed. Retinal layer thicknesses measured with MRI and OCT were analyzed for matching regions of the same eyes close to the optic nerve head.nnnRESULTSnThe temporal SDs of the horizontal and vertical displacements were 78 ± 51 and 130 ± 51 μm (±SD, n = 4), respectively. MRI detected three layers within the human retina, consistent with MRI findings in rodent, feline, and baboon retinas. The hyperintense layer 1 closest to the vitreous likely consisted of nerve fiber, ganglion cell, and inner nuclear layer; the hypointense layer 2, the outer nuclear layer and the inner and outer segments; and the hyperintense layer 3, the choroid. The MRI retina/choroid thickness was 711 ± 37 μm, 19% (P < 0.05) thicker than OCT thickness (579 ± 34 μm).nnnCONCLUSIONSnThis study reports high-resolution MRI of lamina-specific structures in the human retina. These initial results are encouraging. Further improvement in spatiotemporal resolution is warranted.

In vivo depth-resolved oxygen saturation by dual-wavelength photothermal (DWP) OCT

Microvasculature hemoglobin oxygen saturation (SaO2) is important in the progression of various pathologies. Non-invasive depth-resolved measurement of SaO2 levels in tissue microvasculature has the potential to provide early biomarkers and a better understanding of the pathophysiological processes allowing improved diagnostics and prediction of disease progression. We report proof-of-concept in vivo depth-resolved measurement of SaO2 levels in selected 30 µm diameter arterioles in the murine brain using Dual-Wavelength Photothermal (DWP) Optical Coherence Tomography (OCT) with 800 nm and 770 nm photothermal excitation wavelengths. Depth location of back-reflected light from a target arteriole was confirmed using Doppler and speckle contrast OCT images. SaO2 measured in a murine arteriole with DWP-OCT is linearly correlated (R2=0.98) with systemic SaO2 values recorded by a pulse-oximeter. DWP-OCT are steadily lower (10.1%) than systemic SaO2 values except during pure oxygen breathing. DWP-OCT is insensitive to OCT intensity variations and is a candidate approach for in vivo depth-resolved quantitative imaging of microvascular SaO2 levels.

Comparison of pulsed photothermal radiometry, optical coherence tomography and ultrasound for melanoma thickness measurement in PDMS tissue phantoms

Melanoma accounts for 75% of all skin cancer deaths. Pulsed photothermal radiometry (PPTR), optical coherence tomography (OCT) and ultrasound (US) are non-invasive imaging techniques that may be used to measure melanoma thickness, thus, determining surgical margins. We constructed a series of PDMS tissue phantoms simulating melanomas of different thicknesses. PPTR, OCT and US measurements were recorded from PDMS tissue phantoms and results were compared in terms of axial imaging range, axial resolution and imaging time. A Monte Carlo simulation and three-dimensional heat transfer model was constructed to simulate PPTR measurement. Experimental results show that PPTR and US can provide a wide axial imaging range (75 μm-1.7 mm and 120-910 μm respectively) but poor axial resolution (75 and 120 μm respectively) in PDMS tissue phantoms, while OCT has the most superficial axial imaging range (14-450 μm) but highest axial resolution (14 μm). The Monte Carlo simulation and three-dimensional heat transfer model give good agreement with PPTR measurement. PPTR and US are suited to measure thicker melanoma lesions (>400 μm), while OCT is better to measure thin melanoma lesions (<400 μm).

Dual-wavelength photothermal optical coherence tomography for imaging microvasculature blood oxygen saturation

Abstract. A swept-source dual-wavelength photothermal (DWP) optical coherence tomography (OCT) system is demonstrated for quantitative imaging of microvasculature oxygen saturation. DWP-OCT is capable of recording three-dimensional images of tissue and depth-resolved phase variation in response to photothermal excitation. A 1,064-nm OCT probe and 770-nm and 800-nm photothermal excitation beams are combined in a single-mode optical fiber to measure microvasculature hemoglobin oxygen saturation (SO2) levels in phantom blood vessels with a range of blood flow speeds (0 to 17u2009u2009mm/s). A 50-μm-diameter blood vessel phantom is imaged, and SO2 levels are measured using DWP-OCT and compared with values provided by a commercial oximeter at various blood oxygen concentrations. The influences of blood flow speed and mechanisms of SNR phase degradation on the accuracy of SO2 measurement are identified and investigated.

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.

Near infrared femtosecond laser ablation of urinary calculi in water

Pulsed light emitted from a near infrared (λ=800nm) femtosecond laser is capable of plasma induced photodisruption of various materials. We used femtosecond laser pulses to ablate human urinary calculi. Femtosecond pulsed laser interaction with urinary calculi was investigated with various stone compositions, different incident fluences and number of applied pulses. Spectral-domain optical coherence tomography was used to image cross sections of ablation craters on the surface of urinary calculi. Our results indicate that femtosecond laser pulses can ablate various calculi compositions. Crater diameter and depth varies from tens of microns to several hundred microns when up to 1000 pulses were applied. Future studies are required to determine if pulsed near infrared femtosecond laser pulses can be applied clinically for lithotripsy of urinary calculi.

Dual-wavelength photothermal optical coherence tomography for blood oxygen saturation measurement

We report design and demonstration of a dual wavelength photothermal (DWP) optical coherence tomography (OCT) system for imaging of a phantom microvessel and measurement of hemoglobin oxygen saturation (SO2) level. The DWP-OCT system contains a swept-source (SS) two-beam phase-sensitive (PhS) OCT system (1060 nm) and two intensity modulated photothermal excitation lasers (770 nm and 800 nm). The PhS-OCT probe beam (1060 nm) and photothermal excitation beams are combined into one single-mode optical fiber. A galvanometer based two-dimensional achromatic scanning system is designed to provide 14 μm lateral resolution for the PhS-OCT probe beam (1060 nm) and 13 μm lateral resolution for photothermal excitation beams. DWP-OCT system’s sensitivity is 102 dB, axial resolution is 13 μm in tissue and uses a real-time digital dispersion compensation algorithm. Noise floor for optical pathlength measurements is 300 pm in the signal frequency range (380-400 Hz) of photothermal modulation frequencies. Blood SO2 level is calculated from measured optical pathlength (op) signal in a 300 μm diameter microvessel phantom introduced by the two photothermal excitation beams. En-face and B-scan images of a phantom microvessel are recorded, and six blood samples’ SO2 levels are measured using DWP-OCT and compared with values provided by a commercial blood oximeter. A mathematical model indicates thermal diffusion introduces a systematic artifact that over-estimates SO2 values and is consistent with measured data.