Extraction of tissue optical property and blood flow from speckle contrast diffuse correlation tomography (scDCT) measurements

Measurement of blood flow in tissue provides vital information for the diagnosis and therapeutic monitoring of various vascular diseases. A noncontact, camera-based, near-infrared speckle contrast diffuse correlation tomography (scDCT) technique has been recently developed for 3D imaging of blood flow index (αD_B) distributions in deep tissues up to a centimeter. A limitation with the continuous-wave scDCT measurement of blood flow is the assumption of constant and homogenous tissue absorption coefficient (μ_a). The present study took the advantage of rapid, high-density, noncontact scDCT measurements of both light intensities and diffuse speckle contrast at multiple source-detector distances and developed two-step fitting algorithms for extracting both μ_a and αD_B. The new algorithms were tested in tissue-simulating phantoms with known optical properties and human forearms. Measurement results were compared against established near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) techniques. The accuracies of our new fitting algorithms with scDCT measurements in phantoms (up to 16% errors) and forearms (up to 23% errors) are comparable to relevant study results (up to 25% errors). Knowledge of μ_a not only improved the accuracy in calculating αD_B but also provided the potential for quantifying tissue blood oxygenation via spectral measurements. A multiple-wavelength scDCT system with new algorithms is currently developing to fit multi-wavelength and multi-distance data for 3D imaging of both blood flow and oxygenation distributions in deep tissues.     

Broadband miniature optical ultrasound probe for high resolution vascular tissue imaging

An all-optical ultrasound probe for vascular tissue imaging was developed. Ultrasound was generated by pulsed laser illumination of a functionalized carbon nanotube composite coating on the end face of an optical fiber. Ultrasound was detected with a Fabry-Pérot (FP) cavity on the end face of an adjacent optical fiber. The probe diameter was < 0.84 mm and had an ultrasound bandwidth of ~20 MHz. The probe was translated across the tissue sample to create a virtual linear array of ultrasound transmit/receive elements. At a depth of 3.5 mm, the axial resolution was 64 µm and the lateral resolution was 88 µm, as measured with a carbon fiber target. Vascular tissues from swine were imaged ex vivo and good correspondence to histology was observed.OCIS codes: (110.5125) Photoacoustics, (110.2350) Fiber optics imaging, (060.2380) Fiber optics sources and detectors, (170.7170) Ultrasound, (170.0110) Imaging systems     

Optical and dielectric properties of NaCoPO4 in the three phases α, β and γ

In this work, we are interested in the synthesis of monophosphate α-NaCoPO₄, β-NaCoPO₄ and γ-NaCoPO₄ compounds by mechanochemical method and their characterization by X-ray powder diffraction patterns. These compounds are crystallized in the orthorhombic, hexagonal and monoclinic system, in Pnma, P6₅ and P2₁/n space groups, respectively. The optical properties were measured by means of the UV-vis absorption spectrometry in order to deduce the absorption coefficient α and optical band gap E_g. The calculated values of the indirect band gaps (E_gi) for three samples were estimated at 4.71 eV, 4.63 eV and 3.8 for compounds α, β and γ, respectively. The Tauc model was used to determine the optical gap energy of the synthesized compounds. Then, the results of the dielectric proprieties measured by varying the frequency are described.

In this work, we are interested in the synthesis of monophosphate α-NaCoPO₄, β-NaCoPO₄ and γ-NaCoPO₄ compounds by mechanochemical method and their characterization by X-ray powder diffraction patterns.     

Determining the optical properties of a gelatin‑TiO(2) phantom at 780 nm

Tissue phantoms play a central role in validating biomedical imaging techniques. Here we employ a series of methods that aim to fully determine the optical properties, i.e., the refractive index n, absorption coefficient μ_a, transport mean free path ?^?, and scattering coefficient μ_s of a TiO₂ in gelatin phantom intended for use in optoacoustic imaging. For the determination of the key parameters μ_a and ?^?, we employ a variant of time of flight measurements, where fiber optodes are immersed into the phantom to minimize the influence of boundaries. The robustness of the method was verified with Monte Carlo simulations, where the experimentally obtained values served as input parameters for the simulations. The excellent agreement between simulations and experiments confirmed the reliability of the results. The parameters determined at 780 nm are n = 1.359(±0.002), μ^′_s = 1/?^? = 0.22(±0.02)?mm^-1, μ_a= 0.0053(+0.0006-0.0003)?mm^-1, and μ_s = 2.86( ± 0.04)?mm^-1. The asymmetry parameter g obtained from the parameters ?^? and μ^′_s is 0.93, which indicates that the scattering entities are not bare TiO₂ particles but large sparse clusters. The interaction between the scattering particles and the gelatin matrix should be taken into account when developing such phantoms.OCIS codes: (170.3660) Light propagation in tissues, (170.6935) Tissue characterization, (290.1990) Diffusion, (290.4210) Multiple scattering     

Full-depth epidermis tomography using a Mirau-based full-field optical coherence tomography

With a Gaussian-like broadband light source from high brightness Ce³⁺:YAG single-clad crystal fiber, a full-field optical coherence tomography using a home-designed Mirau objective realized high quality images of in vivo and excised skin tissues. With a 40 × silicone-oil-immersion Mirau objective, the achieved spatial resolutions in axial and lateral directions were 0.9 and 0.51 μm, respectively. Such a high spatial resolution enables the separation of lamellar structure of the full epidermis in both the cross-sectional and en face planes. The number of layers of stratum corneum and its thickness were quantitatively measured. This label free and non-invasive optical probe could be useful for evaluating the water barrier of skin tissue in clinics. As a preliminary in vivo experiment, the blood vessel in dermis was also observed, and the flowing of the red blood cells and location of the melanocyte were traced.OCIS codes: (060.2380) Fiber optics sources and detectors, (170.4500) Optical coherence tomography, (160.1435) Biomaterials, (170.3880) Medical and biological imaging, (180.3170) Interference microscopy     

In vivo photothermal optical coherence tomography for non-invasive imaging of endogenous absorption agents

In vivo photothermal optical coherence tomography (OCT) is demonstrated for cross-sectional imaging of endogenous absorption agents. In order to compromise the sensitivity, imaging speed, and sample motion immunity, a new photothermal detection scheme and phase processing method are developed. Phase-resolved swept-source OCT and fiber-pigtailed laser diode (providing excitation at 406 nm) are combined to construct a high-sensitivity photothermal OCT system. OCT probe and excitation beam coaxially illuminate and are focused on tissues. The photothermal excitation and detection procedure is designed to obtain high efficiency of photothermal effect measurement. The principle and method of depth-resolved cross-sectional imaging of absorption agents with photothermal OCT has been derived. The phase-resolved thermal expansion detection algorithm without motion artifact enables in vivo detection of photothermal effect. Phantom imaging with a blood phantom and in vivo human skin imaging are conducted. A phantom with guinea-pig blood as absorber has been scanned by the photothermal OCT system to prove the concept of cross-sectional absorption agent imaging. An in vivo human skin measurement is also performed with endogenous absorption agents.OCIS codes: (110.4500) Optical coherence tomography, (170.6935) Tissue characterization, (350.5340) Photothermal effects, (120.5050) Phase measurement     

Deep,high contrast microscopic cell imaging using three-photon luminescence of β-(NaYF4:Er3+/NaYF4) nanoprobe excited by 1480-nm CW laser of only 1.5-mW

It is challenging to achieve deep microscopic imaging for the strong scattering in biotissue. An efficient three-photon luminescence can effectively increase the penetration depth. Here we report that β-NaYF₄: Er³⁺/NaYF₄ UCNPs were excited by a 1480-nm CW-laser and emitted 543/653-nm light through a three-photon process. With the merit of the hexagonal crystal phase, sub-milliwatt laser power was utilized to excite the UCNP-probed cells to minimize the heating effect. The polymer-coated UCNPs were shown to be harmless to cells. The deep, high contrast in vitro microscopic imaging was implemented through an artificial phantom. Imaging depth of 800 μm was achieved using only 1.5 mW excitation and a 0.7 NA objective. The green/red emission intensities ratio after penetrating the phantom was studied, indicating that longer emission wavelength is preferred for deep multiphoton microscopy. The proposed and demonstrated β-UCNPs would have great potential in three-photon microscopy.OCIS codes: (160.5690) Rare-earth-doped materials, (190.4180) Multiphoton processes, (180.0180) Microscopy     

Sensitivity of frequency-domain optical measurements to brain hemodynamics: simulations and human study of cerebral blood flow during hypercapnia

This study characterizes the sensitivity of noninvasive measurements of cerebral blood flow (CBF) by using frequency-domain near-infrared spectroscopy (FD-NIRS) and coherent hemodynamics spectroscopy (CHS). We considered six FD-NIRS methods: single-distance intensity and phase (SDI and SDϕ), single-slope intensity and phase (SSI and SSϕ), and dual-slope intensity and phase (DSI and DSϕ). Cerebrovascular reactivity (CVR) was obtained from the relative change in measured CBF during a step hypercapnic challenge. Greater measured values of CVR are assigned to a greater sensitivity to cerebral hemodynamics. In a first experiment with eight subjects, CVR_SDϕ was greater than CVR_SDI (p < 0.01), whereas CVR_DSI and CVR_DSϕ showed no significant difference (p > 0.5). In a second experiment with four subjects, a 5 mm scattering layer was added between the optical probe and the scalp tissue to increase the extracerebral layer thickness (L_ec), which caused CVR_DSϕ to become significantly greater than CVR_DSI (p < 0.05). CVR_SS measurements yielded similar results as CVR_DS measurements but with a greater variability, possibly resulting from instrumental artifacts in SS measurements. Theoretical simulations with two-layered media confirmed that, if the top (extracerebral) layer is more scattering than the bottom (brain) layer, the relative values of CVR_DSI and CVR_DSϕ depend on L_ec. Specifically, the sensitivity to the brain is greater for DSI than DSϕ for a thin extracerebral layer (L_ec < 13 mm), whereas it is greater for DSϕ than DSI for a thicker extracerebral layer.     

In-Vivo functional optical-resolution photoacoustic microscopy with stimulated Raman scattering fiber-laser source

In this paper a multi-wavelength optical-resolution photoacoustic microscopy (OR-PAM) system using stimulated Raman scattering is demonstrated for both phantom and in vivo imaging. A 1-ns pulse width ytterbium-doped fiber laser is coupled into a single-mode polarization maintaining fiber. Discrete Raman-shifted wavelength peaks extending to nearly 800 nm are generated with pulse energies sufficient for OR-PAM imaging. Bandpass filters are used to select imaging wavelengths. A dual-mirror galvanometer system was used to scan the focused outputs across samples of carbon fiber networks, 200μm dye-filled tubes, and Swiss Webster mouse ears. Photoacoustic signals were collected in transmission mode and used to create maximum amplitude projection C-scan images. Double dye experiments and in vivo oxygen saturation estimation confirmed functional imaging potential.OCIS codes: (170.3880) Medical and biological imaging, (110.5120) Photoacoustic imaging, (180.5810) Scanning microscopy, (290.5860) Scattering, Raman     

High-speed intravascular photoacoustic imaging at 1.7 μm with a KTP-based OPO

Lipid deposition inside the arterial wall is a hallmark of plaque vulnerability. Based on overtone absorption of C-H bonds, intravascular photoacoustic (IVPA) catheter is a promising technology for quantifying the amount of lipid and its spatial distribution inside the arterial wall. Thus far, the clinical translation of IVPA technology is limited by its slow imaging speed due to lack of a high-pulse-energy high-repetition-rate laser source for lipid-specific first overtone excitation at 1.7 μm. Here, we demonstrate a potassium titanyl phosphate (KTP)-based optical parametric oscillator with output pulse energy up to 2 mJ at a wavelength of 1724 nm and with a repetition rate of 500 Hz. Using this laser and a ring-shape transducer, IVPA imaging at speed of 1 frame per sec was demonstrated. Performance of the IVPA imaging system’s resolution, sensitivity, and specificity were characterized by carbon fiber and a lipid-mimicking phantom. The clinical utility of this technology was further evaluated ex vivo in an excised atherosclerotic human femoral artery with comparison to histology.OCIS codes: (140.3460) Lasers, (110.0110) Imaging systems, (110.5125) Photoacoustics, (170.5120) Photoacoustic imaging, (170.1610) Clinical applications     

Enhanced electrochemical performance of α-MoO3/graphene nanocomposites prepared by an in situ microwave irradiation technique for energy storage applications

Nanoparticles of α-molybdenum oxide (α-MoO₃) are directly grown on graphene sheets using a surfactant-free facile one step ultrafast in situ microwave irradiation method. The prepared α-MoO₃ and α-MoO₃/G nanocomposites are analysed by different characterization techniques to study their structural, morphological and optical properties. Transmission electron microscope images reveal the intercalation of three dimensional (3D) α-MoO₃ nanoparticles into 2D graphene sheets without any agglomeration. The electrochemical results exhibit improved performance for the α-MoO₃/G composite electrode compared to pristine α-MoO₃ owing to its structural superiority. The specific capacitance (C_s) values of the α-MoO₃/G composite and pristine α-MoO₃ are measured to be 483 and 142 F g⁻¹ respectively at a current density of 1 A g⁻¹. The α-MoO₃/G composite maintains a very strong cyclic performance after 5000 cycles. The capacitance retention of the composite electrode shows stable behavior without any degradation confirming its suitability as an enduring electrode material for high-performance supercapacitor applications.

Nanoparticles of α-molybdenum oxide (α-MoO₃) are directly grown on graphene sheets using a surfactant-free facile one step ultrafast in situ microwave irradiation method.     

Miniaturized magnetic-driven scanning probe for endoscopic optical coherence tomography

We designed and implemented a magnetic-driven scanning (MDS) probe for endoscopic optical coherence tomography (OCT). The probe uses an externally-driven tiny magnet in the distal end to achieve unobstructed 360-degree circumferential scanning at the side of the probe. The design simplifies the scanning part inside the probe and thus allows for easy miniaturization and cost reduction. We made a prototype probe with an outer diameter of 1.4 mm and demonstrated its capability by acquiring OCT images of ex vivo trachea and artery samples from a pigeon. We used a spectrometer-based Fourier-domain OCT system and the system sensitivity with our prototype probe was measured to be 91 dB with an illumination power of 850 μW and A-scan exposure time of 1 ms. The axial and lateral resolutions of the system are 6.5 μm and 8.1 μm, respectively.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.2150) Endoscopic imaging, (120.5800) Scanners     

Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure

We present optical coherence micro-elastography, an improved form of compression optical coherence elastography. We demonstrate the capacity of this technique to produce en face images, closely corresponding with histology, that reveal micro-scale mechanical contrast in human breast and lymph node tissues. We use phase-sensitive, three-dimensional optical coherence tomography (OCT) to probe the nanometer-to-micrometer-scale axial displacements in tissues induced by compressive loading. Optical coherence micro-elastography incorporates common-path interferometry, weighted averaging of the complex OCT signal and weighted least-squares regression. Using three-dimensional phase unwrapping, we have increased the maximum detectable strain eleven-fold over no unwrapping and the minimum detectable strain is 2.6 με. We demonstrate the potential of mechanical over optical contrast for visualizing micro-scale tissue structures in human breast cancer pathology and lymph node morphology.OCIS codes: (110.4500) Optical coherence tomography, (110.1650) Coherence imaging, (100.5088) Phase unwrapping     

Anisotropic Kubo conductivity of electric field-induced monolayer β12-borophene

In this paper, we used three monolayer β₁₂-borophene Hamiltonian models to calculate the band structure, intra-band, and inter-band optical conductivity (IOC). Linear response theory and the Kubo formula are employed to calculate optical conductivity. We have shown that the band gap proportional to the inversion non-symmetric model increases by applying an external electric field (EEF), and for homogeneous and inversion-symmetric models, gap opening occurs. We found an anisotropic behavior in the IOC of β₁₂-borophene for polarized light along x and y-directions. The peak of the real part of the IOC for polarized light along the x-direction (ℜσ_xx) locates at the energy equal to the band gap and by applying an EEF shifts to the higher energies and experiences a blue shift. Also, the electric field has little effect on the IOC along y-direction (σ_yy) and in contrast to σ_xx, by applying an electric field, the peak of the IOC shifts towards lower energies and a redshift occurs. In addition, unlike inter-band transitions, the intra-band optical conductivity of β₁₂-borophene is isotropic in all three models, and an EEF can not shift plots to higher or lower energies and only reduces the height of both imaginary and real parts of the optical conductivity.

The optical conductivity of β₁₂-borophene for polarized light along x direction is studied.     

Development of a graded index microlens based fiber optical trap and its characterization using principal component analysis

We demonstrate a miniaturized single beam fiber optical trapping probe based on a high numerical aperture graded index (GRIN) micro-objective lens. This enables optical trapping at a distance of 200μm from the probe tip. The fiber trapping probe is characterized experimentally using power spectral density analysis and an original approach based on principal component analysis for accurate particle tracking. Its use for biomedical microscopy is demonstrated through optically mediated immunological synapse formation.OCIS codes: (060.2310) Fiber optics, (110.2760) Gradient-index lenses, (170.0170) Medical optics and biotechnology, (170.3880) Medical and biological imaging, (170.4520) Optical confinement and manipulation, (180.0180) Microscopy, (180.2520) Fluorescence microscopy, (350.4855) Optical tweezers or optical manipulation     

Extraction of intrinsic fluorescence from single fiber fluorescence measurements on a turbid medium: experimental validation

The detailed mechanisms associated with the influence of scattering and absorption properties on the fluorescence intensity sampled by a single optical fiber have recently been elucidated based on Monte Carlo simulated data. Here we develop an experimental single fiber fluorescence (SFF) spectroscopy setup and validate the Monte Carlo data and semi-empirical model equation that describes the SFF signal as a function of scattering. We present a calibration procedure that corrects the SFF signal for all system-related, wavelength dependent transmission efficiencies to yield an absolute value of intrinsic fluorescence. The validity of the Monte Carlo data and semi-empirical model is demonstrated using a set of fluorescent phantoms with varying concentrations of Intralipid to vary the scattering properties, yielding a wide range of reduced scattering coefficients (μ′_s = 0–7 mm ⁻¹). We also introduce a small modification to the model to account for the case of μ′_s = 0 mm ⁻¹ and show its relation to the experimental, simulated and theoretically calculated value of SFF intensity in the absence of scattering. Finally, we show that our method is also accurate in the presence of absorbers by performing measurements on phantoms containing red blood cells and correcting for their absorption properties.OCIS codes: (060.2310) Fiber optics, (170.6280) Spectroscopy, fluorescence and luminescence     

Photo-responsive polymeric micelles and prodrugs: synthesis and characterization

Bio-recognizable and photocleavable amphiphilic glycopolymers and prodrugs containing photodegradable linkers (i.e. 5-hydroxy-2-nitrobenzyl alcohol) as junction points between bio-recognizable hydrophilic glucose (or maltose) and hydrophobic poly(α-azo-ε-caprolactone)-grafted alkyne or drug chains were synthesized by combining ring-opening polymerization, nucleophilic substitution, and “click” post-functionalization with alkynyl-pyrene and 2-nitrobenzyl-functionalized indomethacin (IMC). The block-grafted glycocopolymers could self-assemble into spherical photoresponsive micelles with hydrodynamic sizes of <200 nm. Fluorescence emission measurements indicated the release of Nile red, a hydrophobic dye, encapsulated by the Glyco-ONB-P(αN₃CL-g-alkyne)_n micelles, in response to irradiation caused by micelle disruption. Light-triggered bursts were observed for IMC-loaded or -conjugated micelles during the first 5 h. Following light irradiation, the drug release rate of IMC-conjugated micelles was faster than that of IMC-loaded micelles. Selective lectin binding experiments confirmed that glycosylated Glyco-ONB-P(αN₃CL-g-alkyne)_n could be used in bio-recognition applications. The nano-prodrug with and without UV irradiation was associated with negligible levels of toxicity at concentrations of less than 30 μg mL⁻¹. The confocal microscopy and flow cytometry results indicated that the uptake of doxorubicin (DOX)-loaded micelles with UV irradiation by HeLa cells was faster than without UV irradiation. The DOX-loaded Gluco-ONB-P(αN₃CL-g-PONBIMC)₁₀ micelles effectively inhibited HeLa cells'' proliferation with a half-maximal inhibitory concentration of 8.8 μg mL⁻¹.

Bio-recognizable and photocleavable amphiphilic glycopolymers and prodrugs containing photodegradable linkers as junction points between hydrophilic glycose and hydrophobic poly(α-azo-ε-caprolactone)-grafted alkyne or drug chains were synthesized.     

Design of miniaturized illumination for transvaginal co-registered photoacoustic and ultrasound imaging

A novel lens-array based illumination design for a compact co-registered photoacoustic/ultrasound transvaginal probe has been demonstrated. The lens array consists of four cylindrical lenses that couple the laser beams into four 1-mm-core multi-mode optical fibers with optical coupling efficiency of ~87%. The feasibility of our lens array was investigated by simulating the lenses and laser beam profiles using Zemax. The laser fluence on the tissue surface was experimentally measured and was below the American National Standards Institute (ANSI) safety limit. Spatial distribution of hemoglobin oxygen saturation (sO₂) of a mouse tumor was obtained in vivo using photoacoustic measurements at multiple wavelengths. Furthermore, benign and malignant ovaries were imaged ex vivo and evaluated histologically. The co-registered images clearly showed different patterns of blood vasculature. These results highlight the clinical potential of our system for noninvasive photoacoustic and ultrasound imaging of ovarian tissue and cancer detection and diagnosis.OCIS codes: (110.0110) Imaging systems, (170.2945) Illumination design, (170.5120) Photoacoustic imaging, (170.6960) Tomography, (170.7170) Ultrasound     

Laser-induced optical breakdown effects of micro-lens arrays and diffractive optical elements on ex vivo porcine skin after 1064 nm picosecond laser irradiation

The current study aims to investigate the effects of micro-lens arrays (MLA) and diffractive optical elements (DOE) on skin tissue via intra-dermal laser-induced optical breakdown (LIOB) after irradiation of 1064-nm picosecond laser light at high energy settings. Irradiation with MLA and DOE was tested on dimming paper, tissue-mimicking phantom, and dark pigmented porcine skin to quantitatively compare distributions of micro-beams, micro-bubbles, and laser-induced vacuoles in the skin. DOE yielded more uniform distributions of the micro-beams on the paper and laser-induced micro-bubbles in the phantom, compared to MLA. The ex vivo skin test confirmed that the DOE-assisted irradiation accompanied more homogeneous generation of the micro-beams on the tissue surface (deviation of ≤ 3%) and a high density of small laser-induced vacuoles (∼78 µm) in the dermis than the MLA-assisted irradiation (deviation of ∼26% and ∼163 µm). The DOE-assisted picosecond laser irradiation may help to achieve deep and uniformly-generated vacuolization under the basal membrane after intra-dermal LIOB for effective fractional skin treatment.