Virtual Hall sensor triggered multi-MHz endoscopic OCT imaging for stable real-time visualization.

Circumferential scanning in endoscopic imaging is crucial across various disciplines, and optical coherence tomography (OCT) is often the preferred choice due to its high-speed, high-resolution, and micron-scale imaging capabilities. Moreover, real-time and high-speed 3D endoscopy is a pivotal technology for medical screening and precise surgical guidance, among other applications. However, challenges such as image jitter and non-uniform rotational distortion (NURD) are persistent obstacles that hinder real-time visualization during high-speed OCT procedures. To address this issue, we developed an innovative, low-cost endoscope that employs a brushless DC motor for scanning, and a sensorless technique for triggering and synchronizing OCT imaging with the scanning motor. This sensorless approach uses the motor's electrical feedback (back electromotive force, BEMF) as a virtual Hall sensor to initiate OCT image acquisition and synchronize it with a Fourier Domain Mode-Locked (FDML)-based Megahertz OCT system. Notably, the implementation of BEMF-triggered OCT has led to a substantial reduction in image jitter and NURD (<4 mrad), thereby opening up a new window for real-time visualization capabilities. This approach suggests potential benefits across various applications, aiming to provide a more accurate, deployable, and cost-effective solution. Subsequent studies can explore the adaptability of this system to specific clinical scenarios and its performance under practical endoscopic conditions.

Dynamic microscopic optical coherence tomography to visualize the morphological and functional micro-anatomy of the airways.

In the imaging of airway tissue, optical coherence tomography (OCT) provides cross-sectional images of tissue structures, shows cilia movement and mucus secretion, but does not provide sufficient contrast to differentiate individual cells. By using fast sequences of microscopic resolution OCT (mOCT) images, OCT can use small signal fluctuations to overcome lack in contrast and speckle noise. In this way, OCT visualizes airway morphology on a cellular level and allows the tracking of the dynamic behavior of immune cells, as well as mucus transport and secretion. Here, we demonstrate that mOCT, by using temporal tissue fluctuation as contrast (dynamic mOCT), provides the possibility to study physiological and pathological tissue processes in vivo.

Dynamic Contrast Microscopic Optical Coherence Tomography As a Novel Method for Assessing Corneal Epithelium During Exposure to Benzalkonium Chloride.

Purpose: Microscopic optical coherence tomography (mOCT) has an imaging resolution of 1 µm in all voxel dimensions, but individual epithelial cells are difficult to resolve due to lack of scattering contrast. Adding dynamic contrast processing to mOCT (dmOCT) results in color images that enable visualization of individual cells and possibly give information on cellular function via the calculation of a motility coefficient. We propose this technique as a novel method of evaluating the ocular surface after exposure to a toxic chemical, benzalkonium chloride (BAK). Methods: Ex vivo cross-section images were acquired with a custom-built, frequency-domain mOCT system. Eyes were explanted from healthy adult C57BL/6 mice and imaged every 30 minutes with five sets of dmOCT scans at each imaging time. Total epithelium and stroma thicknesses were measured from a single mOCT B-scan, and measures of color changes (hue) and the motility coefficient were acquired from dmOCT scans. Results: After 30-minute exposures to 0.005% BAK, local motility decreased and total epithelium thickness increased compared to controls. For basal epithelium cells, local motility decreased after 60-minute exposures, and the hue shifted red after 90-minute exposures. Stroma thickness did not significantly swell until 150-minute exposures to BAK. Conclusions: dmOCT allows us to view the behavior of the cornea epithelium under toxic stress due to BAK, revealing parallel swelling of the extracellular matrix and changes in local subcellular motion. Translational Relevance: The evaluation of the cornea epithelium using dmOCT is helpful to our understanding of the toxic effects of BAK.

Microscopic optical coherence tomography (mOCT) at 600 kHz for 4D volumetric imaging and dynamic contrast.

Volumetric imaging of dynamic processes with microscopic resolution holds a huge potential in biomedical research and clinical diagnosis. Using supercontinuum light sources and high numerical aperture (NA) objectives, optical coherence tomography (OCT) achieves microscopic resolution and is well suited for imaging cellular and subcellular structures of biological tissues. Currently, the imaging speed of microscopic OCT (mOCT) is limited by the line-scan rate of the spectrometer camera and ranges from 30 to 250 kHz. This is not fast enough for volumetric imaging of dynamic processes in vivo and limits endoscopic application. Using a novel CMOS camera, we demonstrate fast 3-dimensional OCT imaging with 600,000 A-scans/s at 1.8 µm axial and 1.1 µm lateral resolution. The improved speed is used for imaging of ciliary motion and particle transport in ex vivo mouse trachea. Furthermore, we demonstrate dynamic contrast OCT by evaluating the recorded volumes rather than en face planes or B-scans. High-speed volumetric mOCT will enable the correction of global tissue motion and is a prerequisite for applying dynamic contrast mOCT in vivo. With further increase in imaging speed and integration in flexible endoscopes, volumetric mOCT may be used to complement or partly replace biopsies.

An Intraoral OCT Probe to Enhanced Detection of Approximal Carious Lesions and Assessment of Restorations.

Caries, the world's most common chronic disease, remains a major cause of invasive restorative dental treatment. To take advantage of the diagnostic potential of optical coherence tomography (OCT) in contemporary dental prevention and treatment, an intraorally applicable spectral-domain OCT probe has been developed based on an OCT hand-held scanner equipped with a rigid 90°-optics endoscope. The probe was verified in vitro. In vivo, all tooth surfaces could be imaged with the OCT probe, except the vestibular surfaces of third molars and the proximal surface sections of molars within a "blind spot" at a distance greater than 2.5 mm from the tooth surface. Proximal surfaces of 64 posterior teeth of four volunteers were assessed by intraoral OCT, visual-tactile inspection, bitewing radiography and fiber-optic transillumination. The agreement in detecting healthy and carious surfaces varied greatly between OCT and established methods (18.2-94.7%), whereby the established methods could always be supplemented by OCT. Direct and indirect composite and ceramic restorations with inherent imperfections and failures of the tooth-restoration bond were imaged and qualitatively evaluated. The intraoral OCT probe proved to be a powerful technological approach for the non-invasive imaging of healthy and carious hard tooth tissues and gingiva as well as tooth-colored restorations.

Dynamic contrast in scanning microscopic OCT.

While optical coherence tomography (OCT) provides a resolution down to 1 µm, it has difficulties in visualizing cellular structures due to a lack of scattering contrast. By evaluating signal fluctuations, a significant contrast enhancement was demonstrated using time-domain full-field OCT (FF-OCT), which makes cellular and subcellular structures visible. The putative cause of the dynamic OCT signal is the site-dependent active motion of cellular structures in a sub-micrometer range, which provides histology-like contrast. Here we demonstrate dynamic contrast with a scanning frequency-domain OCT (FD-OCT), which we believe has crucial advantages. Given the inherent sectional imaging geometry, scanning FD-OCT provides depth-resolved images across tissue layers, a perspective known from histopathology, much faster and more efficiently than FF-OCT. Both shorter acquisition times and tomographic depth-sectioning reduce the sensitivity of dynamic contrast for bulk tissue motion artifacts and simplify their correction in post-processing. Dynamic contrast makes microscopic FD-OCT a promising tool for the histological analysis of unstained tissues.

High-speed fiber scanning endoscope for volumetric multi-megahertz optical coherence tomography.

We present a forward-viewing fiber scanning endoscope (FSE) for high-speed volumetric optical coherence tomography (OCT). The reduction in size of the probe was achieved by substituting the focusing optics by an all-fiber-based imaging system which consists of a combination of scanning single-mode fibers, a glass spacer, made from a step-index multi-mode fiber, and a gradient-index fiber. A lateral resolution of 11 µm was achieved at a working distance of 1.2 mm. The newly designed piezo-based FSE has an outer diameter of 1.6 mm and a rigid length of 13.5 mm. By moving the whole imaging optic in spirals for scanning the sample, the beam quality remains constant over the entire field of view with a diameter of 0.8 mm. The scanning frequency was adjusted to 1.22 kHz for use with a 3.28 MHz Fourier domain mode locked OCT system. Densely sampled volumes have been imaged at a rate of 6 volumes per second.

Novel endoscope with increased depth of field for imaging human nasal tissue by microscopic optical coherence tomography.

Intravital microscopy (IVM) offers the opportunity to visualize static and dynamic changes of tissue on a cellular level. It is a valuable tool in research and may considerably improve clinical diagnosis. In contrast to confocal and non-linear microscopy, optical coherence tomography (OCT) with microscopic resolution (mOCT) provides intrinsically cross-sectional imaging. Changing focus position is not needed, which simplifies especially endoscopic imaging. For in-vivo imaging, here we are presenting endo-microscopic OCT (emOCT). A graded-index-lens (GRIN) based 2.75 mm outer diameter rigid endoscope is providing 1.5 - 2 µm nearly isotropic resolution over an extended field of depth. Spherical and chromatic aberrations are used to elongate the focus length. Simulation of the OCT image formation, suggests a better overall image quality in this range compared to a focused Gaussian beam. Total imaging depth at a reduced sensitivity and lateral resolution is more than 200 µm. Using a frame rate of 80 Hz cross-sectional images of concha nasalis were demonstrated in humans, which could resolve cilial motion, cellular structures of the epithelium, vessels and blood cells. Mucus transport velocity was successfully determined. The endoscope may be used for diagnosis and treatment control of different lung diseases like cystic fibrosis or primary ciliary dyskinesia, which manifest already at the nasal mucosa.

Primary standard for liquid flow rates between 30 and 1500 nl/min based on volume expansion.

An increasing number of microfluidic systems operate at flow rates below 1 µl/min. Applications include (implanted) micropumps for drug delivery, liquid chromatography, and microreactors. For the applications where the absolute accuracy is important, a proper calibration is required. However, with standard calibration facilities, flow rate calibrations below ~1 µl/min are not feasible because of a too large calibration uncertainty. In the current research, a traceable flow rate using a certain temperature increase rate is proposed. When the fluid properties, starting mass, and temperature increase rate are known, this principle yields a direct link to SI units, which makes it a primary standard. In this article, it will be shown that this principle enables flow rate uncertainties in the order of 2-3% for flow rates from 30 to 1500 nl/min.

An experimental setup for traceable measurement and calibration of liquid flow rates down to 5 nl/min.

This work presents the improvements of an experimental setup for measuring ultra-low flow rates down to 5 nl/min. The system uses a telecentric CCD imaging system mounted on a high-precision, computer-controlled linear stage to track a moving liquid meniscus inside a glass capillary. Compared to the original setup, the lowest attainable expanded uncertainty at any flow rate has been reduced from 5.4% to 2%. In addition, the conformity with specification of three commercial micro-fluidic devices was evaluated using the new setup: one syringe pump, one implantable infusion pump and one thermal flow sensor. The flow sensor and the implantable infusion pump met the compliance criteria (coverage probability 95%). The syringe pump however, failed to meet the specifications at 5 nl/min and 10 nl/min. No assessment could be made at higher flow rates.

Synthesis and characterization of a magnetic semiconductor Na(2)RuO(4) containing one-dimensional chains of Ru(6+).

A new ternary ruthenium oxide Na(2)RuO(4) was prepared and shown to crystallize with a new structure type. Single crystal X-ray diffraction measurements reveal that Na(2)RuO(4) consists of RuO(4) chains made up of RuO(5) trigonal bipyramids by sharing axial corners. Na(2)RuO(4) is a magnetic semiconductor with a variable range hopping behavior, and its molar magnetic susceptibility chi(mol) has a broad maximum at approximately 74 K. The derivative d(chi(mol).T)/dT exhibits a peak at 37.7 K which has been confirmed by heat capacity measurement to be due to long-range antiferromagnetic ordering.