Ultra-high-resolution optical coherence tomography for the investigation of thin multilayered pharmaceutical coatings.

Optical Coherence Tomography (OCT) has recently gained attention as a promising technology for in-line monitoring of pharmaceutical film-coating processes for (single-layered) tablet coatings and end-point detection with commercial systems. An increasing interest in the investigation of multiparticulate dosage forms with mostly multi-layered coatings below 20 µm final film thickness demands advancement in OCT technology for pharmaceutical imaging. We present an ultra-high-resolution (UHR-) OCT and investigate its performance based on three different multiparticulate dosage forms with different layer structures (one single-layered, two multi-layered) with layer thicknesses in a range from 5 to 50 µm. The achieved system resolution of 2.4 µm (axial) and 3.4 µm (lateral, both in air) enables the assessment of defects, film thickness variability and morphological features within the coating, previously unattainable using OCT. Despite the high transverse resolution, the provided depth of field was found sufficient to reach the core region of all dosage forms under test. We further demonstrate an automated segmentation and evaluation of UHR-OCT images for coating thicknesses, where human experts struggle using today's standard OCT systems.

Depixelation of coherent fiber bundle imaging by fiber-core-targeted scanning.

A novel fast proximal scanning method, to the best of our knowledge, termed fiber-core-targeted scanning (FCTS), is proposed for illuminating individual fiber cores sequentially to remove the pixelation effect in fiber bundle (FB) imaging. FCTS is based on a galvanometer scanning system. Through a dynamic control of the scan trajectory and speed using the prior knowledge of fiber core positions, FCTS experimentally verifies a precise sequential delivery of laser pulses into fiber cores at a maximal speed of 45,000 cores per second. By applying FCTS on a FB-based photoacoustic forward-imaging probe, the results demonstrate that FCTS eliminates the pixelation effect and improves the imaging quality.

Enhanced medical diagnosis for dOCTors: a perspective of optical coherence tomography.

SIGNIFICANCE: After three decades, more than 75,000 publications, tens of companies being involved in its commercialization, and a global market perspective of about USD 1.5 billion in 2023, optical coherence tomography (OCT) has become one of the fastest successfully translated imaging techniques with substantial clinical and economic impacts and acceptance. AIM: Our perspective focuses on disruptive forward-looking innovations and key technologies to further boost OCT performance and therefore enable significantly enhanced medical diagnosis. APPROACH: A comprehensive review of state-of-the-art accomplishments in OCT has been performed. RESULTS: The most disruptive future OCT innovations include imaging resolution and speed (single-beam raster scanning versus parallelization) improvement, new implementations for dual modality or even multimodality systems, and using endogenous or exogenous contrast in these hybrid OCT systems targeting molecular and metabolic imaging. Aside from OCT angiography, no other functional or contrast enhancing OCT extension has accomplished comparable clinical and commercial impacts. Some more recently developed extensions, e.g., optical coherence elastography, dynamic contrast OCT, optoretinography, and artificial intelligence enhanced OCT are also considered with high potential for the future. In addition, OCT miniaturization for portable, compact, handheld, and/or cost-effective capsule-based OCT applications, home-OCT, and self-OCT systems based on micro-optic assemblies or photonic integrated circuits will revolutionize new applications and availability in the near future. Finally, clinical translation of OCT including medical device regulatory challenges will continue to be absolutely essential. CONCLUSIONS: With its exquisite non-invasive, micrometer resolution depth sectioning capability, OCT has especially revolutionized ophthalmic diagnosis and hence is the fastest adopted imaging technology in the history of ophthalmology. Nonetheless, OCT has not been completely exploited and has substantial growth potential-in academics as well as in industry. This applies not only to the ophthalmic application field, but also especially to the original motivation of OCT to enable optical biopsy, i.e., the in situ imaging of tissue microstructure with a resolution approaching that of histology but without the need for tissue excision.

Ultra-High-Resolution 3D Optical Coherence Tomography Reveals Inner Structures of Human Placenta-Derived Trophoblast Organoids.

OBJECTIVE: 3D optical coherence tomography (OCT) is used for analyses of human placenta organoids in situ without sample preparation. METHODS: The trophoblast organoids analyzed were derived from primary human trophoblast. In this study a custom made ultra-high-resolution spectral domain OCT system with uniform spatial and axial resolution of 2.48 µm in organoid tissue was used. The obtained OCT results align to differentiation status tested via quantitative polymerase chain reaction, Western blot analyses, immunohistochemistry, and immunofluorescence of histological sections. RESULTS: 3D OCT enables a more detailed placenta organoid monitoring compared to brightfield microscopy. Inner architecture with light scattering "bridges" surrounding cavities were visualized and quantified in situ for the first time. The formation of these bridges and cavities is congruent to differentiated trophoblast organoids having developed syncytiotrophoblasts. CONCLUSION: Using 3D OCT in living placenta organoids is a fast tool to assess the differentiation status and resolve internal structures in situ, which is not possible with standard live cell imaging modality. SIGNIFICANCE: Only recently human placenta-derived organoids were established, allowing to have a highly reproducible and stable in vitro model to investigate not only developmental but also physiological and pathophysiological processes during early pregnancy. To our knowledge, this work is the first to analyze living human placenta organoids using 3D OCT. Thereby, the rapid and especially non-endpoint OCT qualitative analyses align to the differentiation stage of organoids, which will aid future advancement in this field.

Ultra-high-resolution SD-OCM imaging with a compact polarization-aligned 840 nm broadband combined-SLED source.

We analyze the influence of intrinsic polarization alignment on image quality and axial resolution employing a broadband 840 nm light source with an optical bandwidth of 160 nm and an output power of 12 mW tailored for spectral-domain optical coherence microscopy (SD-OCM) applications. Three superluminescent diodes (SLEDs) are integrated into a 14-pin butterfly module using a free-space micro-optical bench architecture, maintaining a constant polarization state across the full spectral output. We demonstrate superior imaging performance in comparison to traditionally coupled-SLED broadband light sources in a teleost model organism in-vivo.

Functional optical coherence tomography and photoacoustic microscopy imaging for zebrafish larvae.

We present a dual modality functional optical coherence tomography and photoacoustic microscopy (OCT-PAM) system. The photoacoustic modality employs an akinetic optical sensor with a large imaging window. This imaging window enables direct reflection mode operation, and a seamless integration of optical coherence tomography (OCT) as a second imaging modality. Functional extensions to the OCT-PAM system include Doppler OCT (DOCT) and spectroscopic PAM (sPAM). This functional and non-invasive imaging system is applied to image zebrafish larvae, demonstrating its capability to extract both morphological and hemodynamic parameters in vivo in small animals, which are essential and critical in preclinical imaging for physiological, pathophysiological and drug response studies.

NIR nanoprobe-facilitated cross-referencing manifestation of local disease biology for dynamic therapeutic response assessment.

Pharmacological interventions for effective treatment require opportune, dynamic and accurate manifestation of pathological status. Traditional clinical techniques relying on biopsy-based histological examinations and blood tests are dramatically restricted due to their invasiveness, unsatisfactory precision, non-real-time reporting and risk of complications. Although current strategies through molecular imaging enable non-invasive and spatiotemporal mapping of pathological changes in intact organisms, environment-activatable, sensitive and quantitative sensing platforms, especially for dynamic feedback of the therapeutic response, are still urgently desired in practice. Herein, we innovatively integrate deep-tissue penetrable multispectral optoacoustic tomography (MSOT) and near-infrared (NIR) optical imaging based technology by tailoring a free radical-responsive chromophore with photon-upconverting nanocrystals. During the therapeutic process, the specific reactions between the drug-stimulated reactive oxygen species (ROS) and radical-sensitive probes result in an absorption shift, which can be captured by MSOT. Meanwhile, the radical-triggered reaction also induces multispectral upconversion luminescence (UCL) responses that exhibit the opposite trend in comparison to MSOT. Such reversed-ratiometric dual-modal imaging outcomes provide an ideal cross-referencing system that guarantees the maximum sensing specificity and sensitivity, thus enabling precise disease biology evaluation and treatment assessments in vivo.

Dual modality reflection mode optical coherence and photoacoustic microscopy using an akinetic sensor: publisher's note.

This publisher's note corrects an error in the funding section in Opt. Lett.42, 4319 (2017)OPLEDP0146-959210.1364/OL.42.004319.

Dual modality reflection mode optical coherence and photoacoustic microscopy using an akinetic sensor.

This Letter presents a novel dual modality reflection mode optical coherence and photoacoustic microscopy (OC-PAM) system. The optical coherence microscopy modality features a broadband source to accomplish 5 µm axial resolution. The photoacoustic microscopy modality uses a rigid akinetic Fabry-Perot etalon encapsulated in an optically transparent medium, which forms a 2 mm×11 mm translucent imaging window, permitting reflection mode dual modality imaging. After characterization, the OC-PAM system was applied to image zebrafish larvae in vivo, demonstrating its capability in biomedical imaging with complementary optical scattering and absorption contrasts by revealing morphology in the fish larvae.

Conical scan pattern for enhanced visualization of the human cornea using polarization-sensitive OCT.

Conventional imaging of the human cornea with optical coherence tomography (OCT) relies on telecentric scanning optics with sampling beams that are parallel to the optical axis of the eye. Because of the shape of the cornea, the beams have in some areas considerable inclination to the corneal surface which is accompanied by low signal intensities in these areas and thus an inhomogeneous appearance of corneal structures. In addition, alterations in the polarization state of the probing light depend on the angle between the imaging beam and the birefringent axis of the sample. Therefore, changes in the polarization state observed with polarization-sensitive (PS-) OCT originate mainly from the shape of the cornea. In order to minimize the effects of the corneal shape on intensity and polarization-sensitive based data, we developed a conical scanning optics design. This design provides imaging beams that are essentially orthogonal to the corneal surface. Thus, high signal intensity throughout the entire imaged volume is obtained and the influence of the corneal shape on polarization-sensitive data is greatly reduced. We demonstrate the benefit of the concept by comparing PS-OCT imaging results of the human cornea in healthy volunteers using both scanning schemes.

Multi-directional optical coherence tomography for retinal imaging.

We introduce multi-directional optical coherence tomography (OCT), a technique for investigation of the scattering properties of directionally reflective tissue samples. By combining the concepts of multi-channel and directional OCT, this approach enables simultaneous acquisition of multiple reflectivity depth-scans probing a mutual sample location from differing angular orientations. The application of multi-directional OCT in retinal imaging allows for in-depth investigations on the directional reflectivity of the retinal nerve fiber layer, Henle's fiber layer and the photoreceptor layer. Major ophthalmic diseases (such as glaucoma or age-related macular degeneration) have been reported to alter the directional reflectivity properties of these retinal layers. Hence, the concept of multi-directional OCT might help to gain improved understanding of pathology development and progression. As a first step, we demonstrate the capabilities of multi-directional OCT in the eyes of healthy human volunteers.

Active-passive path-length encoded (APPLE) Doppler OCT.

We present a novel active-passive path-length encoded (APPLE) swept source Doppler optical coherence tomography (DOCT) approach, enabling three-dimensional velocity vector reconstruction of moving particles without prior knowledge of the orientation of motion. The developed APPLE DOCT setup allows for non-invasive blood flow measurements in vivo and was primarily designed for quantitative human ocular blood flow investigations. The system's performance was demonstrated by in vitro flow phantom as well as in vivo retinal vessel bifurcation measurements. Furthermore, total retinal blood flow - a biomarker aiding in diagnosis and monitoring of major ocular diseases such as glaucoma, diabetic retinopathy or central/branch retinal vein occlusion - was determined in the eyes of healthy human volunteers.

Total retinal blood flow measurement by three beam Doppler optical coherence tomography.

We present measurements of total retinal blood flow in healthy volunteers using a three beam Doppler optical coherence tomography (D-OCT) technique. This technology has the advantage of a precise determination of the flow vector without the use of any a-priori information on the vessel geometry. Circular D-OCT scans around the optic disc were recorded and venous as well as arterial total blood flow was determined and compared for each subject. The reproducibility of the method was assessed in 6 subjects by repeated measurements. Only small deviations of around 6% between the measurements were found which indicates the high precision of the proposed method.

Imaging of retinal vasculature using adaptive optics SLO/OCT.

We use our previously developed adaptive optics (AO) scanning laser ophthalmoscope (SLO)/ optical coherence tomography (OCT) instrument to investigate its capability for imaging retinal vasculature. The system records SLO and OCT images simultaneously with a pixel to pixel correspondence which allows a direct comparison between those imaging modalities. Different field of views ranging from 0.8°x0.8° up to 4°x4° are supported by the instrument. In addition a dynamic focus scheme was developed for the AO-SLO/OCT system in order to maintain the high transverse resolution throughout imaging depth. The active axial eye tracking that is implemented in the OCT channel allows time resolved measurements of the retinal vasculature in the en-face imaging plane. Vessel walls and structures that we believe correspond to individual erythrocytes could be visualized with the system.

Single input state polarization sensitive swept source optical coherence tomography based on an all single mode fiber interferometer.

We present a newly developed single mode fiber based swept source polarization sensitive optical coherence tomography system using a single input state at 1040 nm. Two non-polarizing fiber based beam splitters are combined to form a Mach-Zehnder interferometer, while two polarizing beam splitters are used to obtain a polarization sensitive detection. Both types of beam splitters solely feature conventional single mode fibers. Polarization control paddles are used to set and maintain the polarization states in the fibers of the interferometer and detection unit. By use of a special paddle alignment scheme we are able to eliminate any bulk optic wave plates and polarization maintaining fibers in the interferometer and detection paths while preserving the advantages of a single input state system that illuminates the sample with circularly polarized light. To demonstrate the capabilities of our system, we performed retinal measurements on healthy human volunteers.