Photothermal Optical Coherence Tomography Research Articles

Artificial neural network for enhancing signal-to-noise ratio and contrast in photothermal optical coherence tomography

Optical coherence tomography (OCT) is a medical imaging method that generates micron-resolution 3D volumetric images of tissues in-vivo. Photothermal (PT)-OCT is a functional extension of OCT with the potential to provide depth-resolved molecular information complementary to the OCT structural images. PT-OCT typically requires long acquisition times to measure small fluctuations in the OCT phase signal. Here, we use machine learning with a neural network to infer the amplitude of the photothermal phase modulation from a short signal trace, trained in a supervised fashion with the ground truth signal obtained by conventional reconstruction of the PT-OCT signal from a longer acquisition trace. Results from phantom and tissue studies show that the developed network improves signal to noise ratio (SNR) and contrast, enabling PT-OCT imaging with short acquisition times and without any hardware modification to the PT-OCT system. The developed network removes one of the key barriers in translation of PT-OCT (i.e., long acquisition time) to the clinic.

NaYF4:Ho3+/Yb3+@NaGdF4 core@shell upconversion nanoparticles for contrast enhancement in bimodal in-vitro OCT imaging.

Contrast enhancement is exploredin optical coherence tomography images using core NaYF4:Ho3+/Yb3+ and core@shell NaYF4:Ho3+/Yb3+@NaGdF4 nanoparticles. Under 980nm excitation, core@shell nanoparticles exhibited 2.8 and 3.3 times enhancement at 541nm and 646nm emission wavelengths of Ho3+ ions compared to core nanoparticles. Photo-thermal conversion efficiencies were 32% and 20% for core and core@shell nanoparticles. In swept-source optical coherence tomography (SSOCT), core@shell nanoparticles have shown superior contrast, while in photo-thermal optical coherence tomography (PTOCT) core nanoparticles have excelled due to their higher photo-thermal conversion efficiency. The enhancement in contrast to noise ratio obtained is 58dB. Comparative assessments of scattering coefficients and contrast-to-noise ratios were conducted, providing insights into nanoparticle performance for contrast enhancement in optical coherence tomography.

Photothermal optical coherence tomography for 3D live cell detection and mapping.

Imaging cells in their 3D environment with molecular specificity is important to cell biology study. Widely used microscopy techniques, such as confocal microscopy, have limited imaging depth when probing cells in optically scattering media. Optical coherence tomography (OCT) can provide millimeter-level depth for imaging of highly scattering media but lacks the contrast to distinguish cells from extracellular matrix or to distinguish between different types of cells. Photothermal OCT (PT-OCT) is a promising technique to obtain molecular contrast at the imaging scale of OCT. Here, we report PT-OCT imaging of live, nanoparticle-labeled cells in 3D. In particular, we demonstrate detection and mapping of single cell in 3D without causing call death, and show the feasibility of 3D cell mapping through optical scattering media. This work presents live cell detection and mapping at an imaging scale that complements the major microscopy techniques, which is potentially useful to study cells in their 3D native or culture environment.

Exploring the Effect of Size Variability on Efficiency of Upconversion Nanoparticles as Optical Contrast Agents.

The current works explores the optical contrast property and nanaotheranostic capabilities of the rare earth based Upconversion nanoparticles. Optical coherence tomography (OCT) has been used to explore the particles ability to increase contrast and improve signal intensity. Photo thermal OCT, a function extension of OCT has been used to gauge the photo thermal potential of the nanoparticles. The nanoparticles successfully improved contrast and information from the deeper layers of the sample. The particles also showed excellent capability for use as photo thermal agents.

Molecular-Specific Imaging of Tissue with Photo-Thermal Optical Coherence Tomography

Molecular-Specific Imaging of Tissue with Photo-Thermal Optical Coherence Tomography

2D-PROTACs with augmented protein degradation for super-resolution photothermal optical coherence tomography guided momentary multimodal therapy

Proteolytic targeting chimeras (PROTACs) are a strategy for protein degradation through proteasome degradation pathway, which has great potential in nano therapy. However, its degradation efficiency of target protein is low, which could not achieve the expected effect, leading to the failure of this tumor treatment. Herein, Two-dimensional (2D) nanosystems (2D-PROTACs: T-ARV) constructed from tantalum telluride (TaTe2) nanosheets loaded with PROTACs (ARV-825) in order to increase the contact probability between the target protein and E3 ligase and enhance the protein degradation performance. It can realize the efficient degradation of Bromodomain Containing 4 (BRD4) and C-MYC, so as to enhance the photothermal and photodynamic therapy of tumors. Importantly, as a photothermal optical coherence tomography (PT-OCT) contrast agent, T-ARV is able to provide micron-resolution three-dimensional images of tumor tissue, guided multimodal tumor therapy. Therefore, the construction of therapeutic strategies for 2D-PROTACs enables effectively improve the degradation efficiency of protacs to target proteins and enhance the therapeutic effect of nano preparations on tumors.

Three-dimensional opto-thermo-mechanical model for predicting photo-thermal optical coherence tomography responses in multilayer geometries.

Photothermal optical coherence tomography (PT-OCT) is a functional extension of OCT with the ability to generate qualitative maps of molecular absorptions co-registered with the micron-resolution structural tomograms of OCT. Obtaining refined insight into chemical information from PT-OCT images, however, requires solid understanding of the multifactorial physics behind generation of PT-OCT signals and their dependence on system and sample parameters. Such understanding is needed to decouple the various physical effects involved in the PT-OCT signal to obtain more accurate insight into sample composition. In this work, we propose an analytical model that considers the opto-thermo-mechanical properties of multi-layered samples in 3-D space, eliminating several assumptions that have been limiting previous PT-OCT models. In parametric studies, the model results are compared with experimental signals to investigate the effect of sample and system parameters on the acquired signals. The proposed model and the presented findings open the door for: 1) better understanding of the effects of system parameters and tissue opto-thermo-mechanical properties on experimental signals; 2) informed optimization of experimentation strategies based on sample and system parameters; 3) guidance of downstream signal processing for predicting tissue molecular composition.

Carbon Dots with Intrinsic Bioactivities for Photothermal Optical Coherence Tomography, Tumor-Specific Therapy and Postoperative Wound Management.

Carbon dots (CDs) are considered as promising candidates with superior biocompatibilities for multimodel cancer theranostics. However, incorporation of exogenous components, such as targeting molecules and chemo/photo therapeutic drugs, is often required to improve the therapeutic efficacy. Herein, an "all-in-one" CDs that exhibit intrinsic bioactivities for bioimaging, potent tumor therapy, and postoperative management is proposed. The multifunctional CDs derived from gallic acid and tyrosine (GT-CDs) consist of a graphitized carbon core and N, O-rich functional groups, which endow them with a high near-infrared (NIR) photothermal conversion efficiency of 33.9% and tumor-specific cytotoxicity, respectively. A new imaging modality, photothermal optical coherence tomography, is introduced using GT-CDs as the contrast agent, offering the micrometer-scale resolution 3D tissue morphology of tumor. For cancer therapy, GT-CDs initiate the intracellular generation of reactive oxygen species in tumor cells but not normal cells, further induce the mitochondrial collapse and subsequent tumor cellular apoptosis. Combined with NIR photothermal treatment, synergistic antitumor therapy is achieved in vitro and in vivo. GT-CDs also promote the healing process of bacteria-contaminated skin wound, demonstrating their potential to prevent postoperative infection. The integrated theranostic strategy based on versatile GT-CDs supplies an alternative easy-to-handle pattern for disease management.

Synthesis of NaYF4:Ho3+/Yb3+ colloidal upconversion phosphor and its application for OCT-based imaging, temperature sensing, fingerprinting and security ink

In this work, an NaYF4:Ho3+/Yb3+ upconversion phosphor in colloidal form was synthesized and then its suitability for image contrast enhancement in optical coherence tomography (OCT) and photothermal (PT) OCT imaging was analysed.

2d-Protacs with Augmented Protein Degradation for Super-Resolution Photothermal Optical Coherence Tomography Guided Momentary Multimodal Therapy

2d-Protacs with Augmented Protein Degradation for Super-Resolution Photothermal Optical Coherence Tomography Guided Momentary Multimodal Therapy

Transient-mode photothermal optical coherence tomography.

Photothermal optical coherence tomography (PT-OCT) is an emerging extension of OCT, which forms images based on both scattering and absorption of light. The speed of PT-OCT, however, has been limited by the necessity for lock-in detection with extensive temporal sampling of the sample's PT response. Here, we demonstrate transient-mode PT-OCT (TM-PT-OCT), which increases the effective A-line rate by orders of magnitude from 10-100 Hz to 1.5-7.5 kHz, by interrogating the sample's transient thermal response to a single diode laser pulse. Functional imaging of moving samples with TM-PT-OCT at video rate is also presented. This significant improvement in imaging speed is expected to open the door for downstream integration of PT-OCT in clinical systems for in vivo imaging.

Pulse photothermal optical coherence tomography for multimodal hemodynamic imaging.

To realize multimodal hemodynamic imaging, pulse photothermal optical coherence tomography (P-PTOCT) is proposed in this Letter to solve the separation problem of photothermal phase and Doppler phase, which is difficult to solve in traditional PTOCT. This technique can obtain blood flow distribution, light absorption distribution, and concentration images simultaneously. Based on the difference between pulse photothermal phase and Doppler phase, we propose an even number differential demodulation algorithm that can separate the photothermal phase and Doppler phase from the same scanning data set. The separated photothermal phase can characterize the trend of drug concentration, which provides the possibility for quantitative measurement of plasma concentration. The combination of photothermal phase and Doppler phase is helpful for potential clinical research on hemodynamics of cerebral ischemia and provides a technical reference for the rapid acquisition of perfusion volume and plasma concentration at one time.

Polymerically modified superparamagnetic iron oxide nanoparticles as a multi-model molecular probe for functionalized optical coherence tomography

We demonstrate the synthesis, characterization, and potential application of polymerically modified superparamagnetic nanoparticles over bare SPIONs, as a multi-model molecular probe for functionalized optical coherence tomography (fOCT). The synthesized magnetic nanoparticles (MNPs) also have the ability of photo thermionic excitation under near-infrared irradiation (980 nm). By having dual excitation properties, the SPIONs are used as exogenous contrast agents for magnetomotive optical coherence tomography (MMOCT) as well as photothermal optical coherence tomography (PTOCT). We developed a functionalized OCT system and signal processing algorithms for MMOCT and PTOCT. Further, non-invasive in-vivo imaging was performed on swiss-albino mice to demonstrate the potential application of polymerically modified SPIONs. A diffusion dynamics study and contrast-to-noise ratio (CNR) study of the dispersed synthesized SPIONs inside skin tissue of mice as a function of time and depth is also reported. We found that PEG-SPIONs are excellent candidate for molecular contrast agent of functional OCT.

Investigation of Gd2O3: Er3+/Yb3+ Upconversion Nanoparticles (UCNPs) as a Multi-model Contrast Agent for Functional Optical Coherence Tomography (fOCT).

Currently, upconversion nanoparticles (UCNPs) implanted as a contrast agent for optical coherence tomography (OCT) system due to its biocompatibility, anti-stock emission, narrow emission bandwidth non-photobleaching effects etc., but it was not used as multi model imaging probe. We synthesized multimodal imaging probe having upconversion property along with paramagnetic property and used as dual contrast agents for Photothermal Optical Coherence Tomography (PTOCT) and Magnetomotive Optical Coherence Tomography (MMOCT). The synthesized Gd2O3:Er3+/Yb3+ UCNPs shows the bright yellow upconversion emission, biocompatibility with hydrophilic property. A custom built SSOCT setup modified for PTOCT and MMOCT imaging along with custom MATLAB algorithm for signal extraction. A dynamic study was performed with synthesized UCNPs as an imaging probe and functional OCT system for targeted imaging. This shows the utility of the Gd2O3:Er3+/Yb3+ UCNPs as molecular probe for targeted imaging applications.

Ex-vivo molecular imaging with upconversion nanoparticles (UCNPs) using photo thermal optical coherence tomography (PTOCT).

We demonstrate a photothermal optical coherence tomography (PTOCT) system, with upconversion nanoparticles (UCNPs) as a molecular probe. We synthesized hydrophilic, biocompatible upconversion nanoparticles (UCNPs) using hydrothermal synthesis. We developed the PTOCT system along with the signal processing tool and applied this technique on animal tissue phantom for targeted imaging. The 'lock-in detection' of the amplitude modulated photothermal beam (980 nm), which used to excite the UCNPs was the backbone of the signal processing algorithm. The signal processing was further established in different aspects. As an application part, the diffusion dynamics of the UCNPs was performed inside the tissue to study molecular movement and subsequent changes in tissue properties. A comparison of photothermal optical coherence tomography (PTOCT) with phase variance optical coherence tomography (PVOCT) for targeted molecular imaging also presented.

Redox responsive nanoparticle encapsulating black phosphorus quantum dots for cancer theranostics

Effective cancer treatment puts high demands for cancer theranostics. For cancer diagnostics, optical coherence tomography (OCT) technology (including photothermal optical coherence tomography (PT-OCT)) has been widely investigated since it induces changes in optical phase transitions in tissue through environmental changes (such as temperature change for PT-OCT). In this report, redox responsive nanoparticle encapsulating black phosphorus quantum dots was developed as a robust PT-OCT agent. Briefly, black phosphorus quantum dots (BPQDs) are incorporated into cysteine-based poly-(disulfide amide) (Cys-PDSA) to form stable and biodegradable nanoagent. The excellent photothermal feature allows BPQD/Cys-PDSA nanoparticles (NPs) as a novel contrast agent for high-resolution PT-OCT bioimaging. The Cys-PDSA can rapidly respond to glutathione and effectively release BPQDs and drugs in vitro and in vivo. And the obtained NPs exhibit excellent near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity that can serve as novel therapeutic platform, with very low chemo drug dosage and side effects. Both of the polymer and BPQD are degradable, indicating this platform is a rare PT-OCT agent that is completely biodegradable. Overall, our research highlights a biodegradable and biocompatible black phosphorus-based nanoagent for both cancer diagnosis and therapy.

Methylene blue-filled biodegradable polymer particles as a contrast agent for optical coherence tomography.

Optical coherence tomography (OCT) images largely lack molecular information or molecular contrast. We address that issue here, reporting on the development of biodegradable micro and nano-spheres loaded with methylene blue (MB) as molecular contrast agents for OCT. MB is a constituent of FDA approved therapies and widely used as a dye in off-label clinical applications. The sequestration of MB within the polymer reduced toxicity and improved signal strength by drastically reducing the production of singlet oxygen and leuco-MB. The former leads to tissue damage and the latter to reduced image contrast. The spheres are also strongly scattering which improves molecular contrast signal localization and enhances signal strength. We demonstrate that these contrast agents may be imaged using both pump-probe OCT and photothermal OCT, using a 830 nm frequency domain OCT system and a 1.3 µm swept source OCT system. We also show that these contrast agents may be functionalized and targeted to specific receptors, e.g. the VCAM receptor known to be overexpressed in inflammation.

基于光热光学相干层析技术的肿瘤组织三维成像

基于光热光学相干层析技术的肿瘤组织三维成像

Hyperspectral optical coherence tomography for in vivo visualization of melanin in the retinal pigment epithelium.

Previous studies for melanin visualization in the retinal pigment epithelium (RPE) have exploited either its absorption properties (using photoacoustic tomography or photothermal optical coherence tomography [OCT]) or its depolarization properties (using polarization sensitive OCT). However, these methods are only suitable when the melanin concentration is sufficiently high. In this work, we present the concept of hyperspectral OCT for melanin visualization in the RPE when the concentration is low. Based on white light OCT, a hyperspectral stack of 27 wavelengths (440‐700 nm) was created in post‐processing for each depth‐resolved image. Owing to the size and shape of the melanin granules in the RPE, the variations in backscattering coefficient as a function of wavelength could be identified—a result which is to be expected from Mie theory. This effect was successfully identified both in eumelanin‐containing phantoms and in vivo in the low‐concentration Brown Norway rat RPE.

Photothermal optical coherence tomography for investigation and imaging photothermal trapping of gold nano-rods in clear media and biological tissue

A quantitative spectrometer-based photothermal optical coherence tomography (PT-OCT) system is employed to investigate and image the photothermal trapping of gold nano-rods (GNRs) in clear and biological media. The PT-OCT system is calibrated through dynamic phase measurements of piezo motion with known driving parameters. We measure and compare the displacement sensitivities of the PT-OCT system at different camera exposure time settings in two configurations: with a distinct reference path; and with a common path. The displacement sensitivity of the system in the common path configuration is improved from 1.5 to 0.17 nm by performing Fourier analysis on the output phase. The minimum Ti:Sa power capable of inducing a detectable photothermal response of GNRs is measured to be 0.5 mW. This value agrees with the latest reported minimum Ti:Sa power for photothermal trapping GNRs. The PT-OCT system is used to generate en-face images of photothermal trapped GNRs in the water solution and in the biological tissue. By displaying the difference between successive en-face phase images, spatial distribution patterns of the aggregated GNRs, resulted from the photothermal trapping, are clearly outlined with great contrast. The photothermal trapping of GNRs in tissue shows a greater complexity than in the clear media. The limitation of the PT-OCT technology is discussed. The study proves the potential of PT-OCT for imaging the photothermal trapping of GNRs.