Investigation of Laser-Induced Periodic Surface Structures Using Synthetic Optical Holography.

In this paper, the investigation of laser-induced periodic surface structures (LIPSSs) on a polycrystalline diamond substrate using synthetic optical holography (SOH) is demonstrated. While many techniques for LIPSS detection operate with sample contact and/or require preparation or processing of the sample, this novel technique operates entirely non-invasively without any processing of or contact with the LIPSS sample at all. The setup provides holographic amplitude and phase images of the investigated sample with confocally enhanced and diffraction-limited lateral resolution, as well as three-dimensional surface topography images of the periodic structures via phase reconstruction with one single-layer scan only.

Applying machine learning to optical coherence tomography images for automated tissue classification in brain metastases.

PURPOSE: A precise resection of the entire tumor tissue during surgery for brain metastases is essential to reduce local recurrence. Conventional intraoperative imaging techniques all have limitations in detecting tumor remnants. Therefore, there is a need for innovative new imaging methods such as optical coherence tomography (OCT). The purpose of this study is to discriminate brain metastases from healthy brain tissue in an ex vivo setting by applying texture analysis and machine learning algorithms for tissue classification to OCT images. METHODS: Tumor and healthy tissue samples were collected during resection of brain metastases. Samples were imaged using OCT. Texture features were extracted from B-scans. Then, a machine learning algorithm using principal component analysis (PCA) and support vector machines (SVM) was applied to the OCT scans for classification. As a gold standard, an experienced pathologist examined the tissue samples histologically and determined the percentage of vital tumor, necrosis and healthy tissue of each sample. A total of 14.336 B-scans from 14 tissue samples were included in the classification analysis. RESULTS: We were able to discriminate vital tumor from healthy brain tissue with an accuracy of 95.75%. By comparing necrotic tissue and healthy tissue, a classification accuracy of 99.10% was obtained. A generalized classification between brain metastases (vital tumor and necrosis) and healthy tissue was achieved with an accuracy of 96.83%. CONCLUSIONS: An automated classification of brain metastases and healthy brain tissue is feasible using OCT imaging, extracted texture features and machine learning with PCA and SVM. The established approach can prospectively provide the surgeon with additional information about the tissue, thus optimizing the extent of tumor resection and minimizing the risk of local recurrences.

Digital holography for spatially resolved analysis of the semiconductor optical response.

We present spatially resolved measurements of the below-band-gap carrier-induced absorption and concurrent phase change in a semiconductor with the help of transmission digital holography. The application is demonstrated for a bulk GaAs sample, while the holograms are recorded with a conventional CMOS sensor. We show that the phase information enables spatially resolved monitoring of excess carrier distributions. Based on that, we discuss a phase-based approach for separation of carrier and heat related effects in the semiconductor optical response.

Confocal laser scanning holographic microscopy of buried structures.

In this paper, we present a confocal laser scanning holographic microscope for the investigation of buried structures. The multimodal system combines high diffraction limited resolution and high signal-to-noise-ratio with the ability of phase acquisition. The amplitude and phase imaging capabilities of the system are shown on a test target. For the investigation of buried integrated semiconductor structures, we expand our system with an optical beam induced current modality that provides additional structure-sensitive contrast. We demonstrate the performance of the multimodal system by imaging the buried structures of a microcontroller through the silicon backside of its housing in reflection geometry.

Femtosecond pulse generation from external cavity diode laser based on self-mode-locking.

In this Letter, we report optical pulse generation from a single-section diode gain chip, employed in an external cavity geometry based on the self-mode-locking regime. The gain chip emits light at 1550 nm wavelength range. The external cavity is operated at various repetition rates, ranging from 1 to 2.5 GHz. An optical pulse width of approximately 650 fs is obtained by fitting a Lorentzian distribution. A low RF spectral width of 78.875 kHz is measured corresponding to a low pulse-to-pulse RMS timing jitter of 1.273 ps. This system paves the way towards ultra-compact, cost-effective, and chirp-compensated femtosecond laser pulse sources with adjustable repetition rates.

Lensless digital holographic microscopy as an efficient method to monitor enzymatic plastic degradation.

A big challenge of the 21st century is to cope with the huge amounts of plastic waste on Earth. Especially the oceans are heavily polluted with plastics. To counteract this issue, biological (enzymatic) plastic decomposition is increasingly gaining attention. Recently it was shown that polyethylene terephthalate (PET) can be degraded in a saltwater-based environment using bacterial PETase produced by a marine diatom. At moderate temperatures, plastic biodegradation is slow and requires sensitive methods for detection, at least at initial stages. However, conventional methods for verifying the plastic degradation are either complex, expensive, time-consuming or they interfere with the degradation process. Here, we adapt lensless digital holographic microscopy (LDHM) as a new application for efficiently monitoring enzymatic degradation of a PET glycol copolymer (PETG). LDHM is a cost-effective, compact and sensitive optical method. We demonstrate enzymatic PETG degradation over a time course of 43 days employing numerical analysis of LDHM images.

Prostate Cancer Foundation Hormone-Sensitive Prostate Cancer Biomarker Working Group Meeting Summary.

Androgen deprivation therapy remains the backbone therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, several treatments, including docetaxel, abiraterone + prednisone, enzalutamide, and apalutamide, have each been shown to demonstrate survival benefit when used upfront along with androgen deprivation therapy. However, treatment selection for an individual patient remains a challenge. There is no high level clinical evidence for treatment selection among these choices based on biological drivers of clinical disease. In August 2020, the Prostate Cancer Foundation convened a working group to meet and discuss biomarkers for hormone-sensitive prostate cancer, the proceedings of which are summarized here. This meeting covered the state of clinical and biological evidence for systemic therapies in the mHSPC space, with emphasis on charting a course for the generation, interrogation, and clinical implementation of biomarkers for treatment selection.

Two-photon polymerization with diode lasers emitting ultrashort pulses with high repetition rate.

In this Letter, we investigate the resolution of two-photon polymerization (2PP) with an amplified mode-locked external cavity diode laser with adjustable pulse length and a high repetition rate. The experimental results are analyzed with a newly developed 2PP model. Even with low pulse peak intensity, the produced structural dimensions are comparable to those generated by traditional 2PP laser sources. Thus, we show that a compact monolithic picosecond laser diode without amplification and with a repetition rate in the GHz regime can also be applied for 2PP. These results show the high application potential of compact mode-locked diode lasers for low-cost and compact 2PP systems.

Monitoring of photochemically induced changes in phase-modulating samples with digital holographic microscopy.

This paper analyzes the performance of single-shot digital holographic microscopy for rapid characterization of static step-index structures in transparent polymer materials and for online monitoring of the photoinduced polymerization dynamics. The experiments are performed with a modified Mach-Zehnder transmission digital holographic microscope of high stability (phase accuracy of 0.69°) and of high magnification (of ≈90×). Use of near-infrared illumination allows both nondestructive examination of the manufactured samples and monitoring of optically induced processes in a photosensitive material concurrently with its excitation. The accuracy of the method for a precise sample's topography evaluation is studied on an example of microchannel sets fabricated via two-photon polymerization and is supported by reference measurements with an atomic force microscope. The applicability of the approach for dynamic measurements is proved via online monitoring of the refractive index evolution in a photoresin layer illuminated with a focused laser beam at 405 nm. High correlation between the experimental results and a kinetics model for the photopolymerization process is achieved.

Comparison between optical coherence tomography imaging and histological sections of peripheral nerves.

OBJECTIVE: Optical coherence tomography (OCT) is an imaging technique that uses the light-backscattering properties of different tissue types to generate an image. In an earlier feasibility study the authors showed that it can be applied to visualize human peripheral nerves. As a follow-up, this paper focuses on the interpretation of the images obtained. METHODS: Ten different short peripheral nerve specimens were retained following surgery. In a first step they were examined by OCT during, or directly after, surgery. In a second step the nerve specimens were subjected to histological examination. Various steps of image processing were applied to the OCT raw data acquired. The improved OCT images were compared with the sections stained by H & E. The authors assigned the structures in the images to the various nerve components including perineurium, fascicles, and intrafascicular microstructures. RESULTS: The results show that OCT is able to resolve the myelinated axons. A weighted averaging filter helps in identifying the borders of structural features and reduces artifacts at the same time. Tissue-remodeling processes due to injury (perineural fibrosis or neuroma) led to more homogeneous light backscattering. Anterograde axonal degeneration due to sharp injury led to a loss of visible axons and to an increase of light-backscattering tissue as well. However, the depth of light penetration is too small to allow generation of a complete picture of the nerve. CONCLUSIONS: OCT is the first in vivo imaging technique that is able to resolve a nerve's structures down to the level of myelinated axons. It can yield information about focal and segmental pathologies.

Transducer-matched multipulse excitation for signal-to-noise ratio improvement in diode laser-based photoacoustic systems.

We analyze transducer-matched multipulse excitation as a method for improving of the signal-to-noise ratio (SNR) for diode laser-based photoacoustic systems. We discuss the principle of the technique, its advantages, and potential drawbacks and perform measurements to analyze the obtainable SNR increase. We show in experiment and computationally that a lower boundary estimate of 1.2 to 1.8 fold SNR improvement can be provided using transducer-matched pulse bursts, depending on the transducer and particular arrangement. Finally, we analyze implications that the transducer resonance effects may have on the recently introduced advanced photoacoustic techniques. The findings are of immediate interest to modalities utilizing dense pulse sequences and systems possessing limited pulse energy. In particular, transducer-matched multipulse excitation may be beneficial for diode-based photoacoustic systems operated with transducers in the range of 1 to 5 MHz since the required hardware is readily available.

Ultrafast spin-lasers.

Lasers have both ubiquitous applications and roles as model systems in which non-equilibrium and cooperative phenomena can be elucidated1. The introduction of novel concepts in laser operation thus has potential to lead to both new applications and fundamental insights2. Spintronics3, in which both the spin and the charge of the electron are used, has led to the development of spin-lasers, in which charge-carrier spin and photon spin are exploited. Here we show experimentally that the coupling between carrier spin and light polarization in common semiconductor lasers can enable room-temperature modulation frequencies above 200 gigahertz, exceeding by nearly an order of magnitude the best conventional semiconductor lasers. Surprisingly, this ultrafast operation of the resultant spin-laser relies on a short carrier spin relaxation time and a large anisotropy of the refractive index, both of which are commonly viewed as detrimental in spintronics3 and conventional lasers4. Our results overcome the key speed limitations of conventional directly modulated lasers and offer a prospect for the next generation of low-energy ultrafast optical communication.

Automated differentiation between meningioma and healthy brain tissue based on optical coherence tomography ex vivo images using texture features.

Brain tissue analysis is highly desired in neurosurgery, such as tumor resection. To guarantee best life quality afterward, exact navigation within the brain during the surgery is essential. So far, no method has been established that perfectly fulfills this need. Optical coherence tomography (OCT) is a promising three-dimensional imaging tool to support neurosurgical resections. We perform a preliminary study toward in vivo brain tumor removal assistance by investigating meningioma, healthy white, and healthy gray matter. For that purpose, we utilized a commercially available OCT device (Thorlabs Callisto) and measured eight samples of meningioma, three samples of healthy white, and two samples of healthy gray matter ex vivo directly after removal. Structural variations of different tissue types, especially meningioma, can already be seen in the raw OCT images. Nevertheless, an automated differentiation approach is desired, so that neurosurgical guidance can be delivered without a-priori knowledge of the surgeon. Therefore, we employ different algorithms to extract texture features and apply pattern recognition methods for their classification. With these postprocessing steps, an accuracy of nearly 98% was found.

High-resolution 3D light fluence mapping for heterogeneous scattering media by localized sampling.

We demonstrate an innovative concept for three-dimensional optical fluence mapping in heterogeneous highly scattering media as, e.g., biomedical tissues. We propose to use the relative light extinction analysis principle together with a miniaturized collection fiber in a direct fluence measurement setup as a method to obtain the spatially resolved light intensity distribution under transversally inhomogeneous light propagation conditions and provide local characterization of the transport medium. System performance is validated in two extreme conditions: an optically thin scattering medium and an absorption-dominated light transport. Both extremes demonstrate good agreement to theoretical expectations. Finally, we successfully prove the ability of the system to deliver high-resolution fluence maps through a model study of the light distribution induced in a scattering medium by a vertical diode laser stack with individual bars pitched only 500 µm apart.

Femtosecond semiconductor laser system with resonator-internal dispersion adaptation.

We present a femtosecond laser diode system that is capable of autonomously adjusting itself to compensate for the external dispersion in an arbitrary application. The laser system contains a spatial light modulator inside the cavity which is controlled by an evolutionary algorithm in order to allow for phase and amplitude shaping of the laser emission. The cavity-internal dispersion control is shown to be much more efficient than an external control with a pulse shaper.

Patient-Reported Outcome Measures: How Do Digital Tablets Stack Up to Paper Forms? A Randomized, Controlled Study.

Patient-reported outcomes (PROs) are essential to assessing the effectiveness of care, and many general-health and disease-specific PROs have been developed. Until recently, data were collected predominantly with pen-and-paper questionnaires. Now, though, there is a potential role for electronic medical records in data collection. In this study, patients were randomly assigned to complete either tablet or paper questionnaires. They were surveyed on patient demographics, patterns of electronic device use, general-health and disease-specific PROs, and satisfaction. The primary outcome measure was survey completion rate. Secondary outcome measures were total time for completion, number of questions left unanswered on incomplete surveys, patient satisfaction, and survey preferences. The study included 483 patients (258 in tablet group, 225 in paper group), and the overall completion rate was 84.4%. There was no significant difference in PRO completion between the tablet and paper groups. Time to completion did not differ between the groups, but their satisfaction rates were similar. However, more paper group patients reported a preference for a tablet survey. Advantages of digital data collection include simple and reliable data storage, ability to improve completion rates by requiring patients to answer all questions, and development of interface adaptations to accommodate patients with handicaps. Given our data and these theoretical benefits, we recommend using tablet data collection systems for PROs.

Self-optimizing femtosecond semiconductor laser.

A self-optimizing approach to intra-cavity spectral shaping of external cavity mode-locked semiconductor lasers using edge-emitting multi-section diodes is presented. An evolutionary algorithm generates spectrally resolved phase- and amplitude masks that lead to the utilization of a large part of the net gain spectrum for mode-locked operation. Using these masks as a spectral amplitude and phase filter, a bandwidth of the optical intensity spectrum of 3.7 THz is achieved and Fourier-limited pulses of 216 fs duration are generated after further external compression.

Development and evaluation of a device for simultaneous uniaxial compression and optical imaging of cartilage samples in vitro.

In this paper, we present a system that allows imaging of cartilage tissue via optical coherence tomography (OCT) during controlled uniaxial unconfined compression of cylindrical osteochondral cores in vitro. We describe the system design and conduct a static and dynamic performance analysis. While reference measurements yield a full scale maximum deviation of 0.14% in displacement, force can be measured with a full scale standard deviation of 1.4%. The dynamic performance evaluation indicates a high accuracy in force controlled mode up to 25 Hz, but it also reveals a strong effect of variance of sample mechanical properties on the tracking performance under displacement control. In order to counterbalance these disturbances, an adaptive feed forward approach was applied which finally resulted in an improved displacement tracking accuracy up to 3 Hz. A built-in imaging probe allows on-line monitoring of the sample via OCT while being loaded in the cultivation chamber. We show that cartilage topology and defects in the tissue can be observed and demonstrate the visualization of the compression process during static mechanical loading.

Multiwavelength phase unwrapping and aberration correction using depth filtered digital holography.

In this Letter, we present a new approach to processing data from a standard spectral domain optical coherence tomography (OCT) system using depth filtered digital holography (DFDH). Intensity-based OCT processing has an axial resolution of the order of a few micrometers. When the phase information is used to obtain optical path length differences, subwavelength accuracy can be achieved, but this limits the resolvable step heights to half of the wavelength of the system. Thus there is a metrology gap between phase- and intensity-based methods. Our concept addresses this metrology gap by combining DFHD with multiwavelength phase unwrapping. Additionally, the measurements are corrected for aberrations. Here, we present proof of concept measurements of a structured semiconductor sample.

Mode-locked semiconductor laser system with intracavity spatial light modulator for linear and nonlinear dispersion management.

We analyze the influence of second and third order intracavity dispersion on a passively mode-locked diode laser by introducing a spatial light modulator (SLM) into the external cavity. The dispersion is optimized for chirped pulses with highest possible spectral bandwidth that can be externally compressed to the sub picosecond range. We demonstrate that the highest spectral bandwidth is achieved for a combination of second and third order dispersion. With subsequent external compression pulses with a duration of 437 fs are generated.