Depth-Resolved Localization Microangiography in the NIR-II Window.

Detailed characterization of microvascular alterations requires high-resolution 3D imaging methods capable of providing both morphological and functional information. Existing optical microscopy tools are routinely used for microangiography, yet offer suboptimal trade-offs between the achievable field of view and spatial resolution with the intense light scattering in biological tissues further limiting the achievable penetration depth. Herein, a new approach for volumetric deep-tissue microangiography based on stereovision combined with super-resolution localization imaging is introduced that overcomes the spatial resolution limits imposed by light diffusion and optical diffraction in wide-field imaging configurations. The method capitalizes on localization and tracking of flowing fluorescent particles in the second near-infrared window (NIR-II, ≈1000-1700 nm), with the third (depth) dimension added by triangulation and stereo-matching of images acquired with two short-wave infrared cameras operating in a dual-view mode. The 3D imaging capability enabled with the proposed method facilitates a detailed visualization of microvascular networks and an accurate blood flow quantification. Experiments performed in tissue-mimicking phantoms demonstrate that high resolution is preserved up to a depth of 4 mm in a turbid medium. Transcranial microangiography of the entire murine cortex and penetrating vessels is further demonstrated at capillary level resolution.

Enhancing optoacoustic mesoscopy through calibration-based iterative reconstruction.

Optoacoustic mesoscopy combines rich optical absorption contrast with high spatial resolution at tissue depths beyond reach for microscopic techniques employing focused light excitation. The mesoscopic imaging performance is commonly hindered by the use of inaccurate delay-and-sum reconstruction approaches and idealized modeling assumptions. In principle, image reconstruction performance could be enhanced by simulating the optoacoustic signal generation, propagation, and detection path. However, for most realistic experimental scenarios, the underlying total impulse response (TIR) cannot be accurately modelled. Here we propose to capture the TIR by scanning of a sub-resolution sized absorber. Significant improvement of spatial resolution and depth uniformity is demonstrated over 3 mm range, outperforming delay-and-sum and model-based reconstruction implementations. Reconstruction performance is validated by imaging subcutaneous murine vasculature and human skin in vivo. The proposed experimental calibration and reconstruction paradigm facilitates quantitative inversions while averting complex physics-based simulations. It can readily be applied to other imaging modalities employing TIR-based reconstructions.

Rapid functional optoacoustic micro-angiography in a burst mode.

Optoacoustic microscopy (OAM) can image intrinsic optical absorption contrast at depths of several millimeters where state-of-the-art optical microscopy techniques fail due to intense light scattering in living tissues. Yet, wide adoption of OAM in biology and medicine is hindered by slow image acquisition speed, small field of view (FOV), and/or lack of spectral differentiation capacity of common system implementations. We report on a rapid acquisition functional optoacoustic micro-angiography approach that employs a burst-mode laser triggering scheme to simultaneously acquire multi-wavelength 3D images over an extended FOV covering ${50}\;{\rm mm} \times {50}\;{\rm mm}$50mm×50mm in a single mechanical overfly scan, attaining 28 µm and 14 µm resolution in lateral and axial dimensions, respectively. Owing to an ultrawideband low-noise design featuring a spherically focused polyvinylidene difluoride transducer, we demonstrate imaging of human skin and underlying vasculature at up to 3.8 mm depth when using per-pulse laser energies of only 25 µJ without employing signal averaging. Overall, the developed system greatly enhances performance and usability of OAM for dermatologic and micro-angiographic studies.

Remote Actuation Systems for Fully Wearable Assistive Devices: Requirements, Selection, and Optimization for Out-of-the-Lab Application of a Hand Exoskeleton.

Wearable robots assist individuals with sensorimotor impairment in daily life, or support industrial workers in physically demanding tasks. In such scenarios, low mass and compact design are crucial factors for device acceptance. Remote actuation systems (RAS) have emerged as a popular approach in wearable robots to reduce perceived weight and increase usability. Different RAS have been presented in the literature to accommodate for a wide range of applications and related design requirements. The push toward use of wearable robotics in out-of-the-lab applications in clinics, home environments, or industry created a shift in requirements for RAS. In this context, high durability, ergonomics, and simple maintenance gain in importance. However, these are only rarely considered and evaluated in research publications, despite being drivers for device abandonment by end-users. In this paper, we summarize existing approaches of RAS for wearable assistive technology in a literature review and compare advantages and disadvantages, focusing on specific evaluation criteria for out-of-the-lab applications to provide guidelines for the selection of RAS. Based on the gained insights, we present the development, optimization, and evaluation of a cable-based RAS for out-of-the-lab applications in a wearable assistive soft hand exoskeleton. The presented RAS features full wearability, high durability, high efficiency, and appealing design while fulfilling ergonomic criteria such as low mass and high wearing comfort. This work aims to support the transfer of RAS for wearable robotics from controlled lab environments to out-of-the-lab applications.

High-Throughput Platform for Optoacoustic Probing of Genetically Encoded Calcium Ion Indicators.

Functional optoacoustic (OA) imaging assisted with genetically encoded calcium ion indicators (GECIs) holds promise for imaging large-scale neuronal activity at depths and spatiotemporal resolutions not attainable with existing optical microscopic techniques. However, currently available GECIs optimized for fluorescence (FL) imaging lack sufficient contrast for OA imaging and respond at wavelengths having limited penetration into the mammalian brain. Here we present an imaging platform capable of rapid assessment and cross-validation between OA and FL responses of sensor proteins expressed in Escherichia coli colonies. The screening system features optimized pulsed light excitation combined with ultrasensitive ultrasound detection to mitigate photobleaching while further allowing the dynamic characterization of calcium ion responses with millisecond precision. Targeted probing of up to six individual colonies per second in both calcium-loaded and calcium-unloaded states was possible with the system. The new platform greatly facilitates optimization of absorption-based labels, thus setting the stage for directed evolution of OA GECIs.

Patient-specific in silico models can quantify primary implant stability in elderly human bone.

Secure implant fixation is challenging in osteoporotic bone. Due to the high variability in inter- and intra-patient bone quality, ex vivo mechanical testing of implants in bone is very material- and time-consuming. Alternatively, in silico models could substantially reduce costs and speed up the design of novel implants if they had the capability to capture the intricate bone microstructure. Therefore, the aim of this study was to validate a micro-finite element model of a multi-screw fracture fixation system. Eight human cadaveric humerii were scanned using micro-CT and mechanically tested to quantify bone stiffness. Osteotomy and fracture fixation were performed, followed by mechanical testing to quantify displacements at 12 different locations on the instrumented bone. For each experimental case, a micro-finite element model was created. From the micro-finite element analyses of the intact model, the patient-specific bone tissue modulus was determined such that the simulated apparent stiffness matched the measured stiffness of the intact bone. Similarly, the tissue modulus of a small damage region around each screw was determined for the instrumented bone. For validation, all in silico models were rerun using averaged material properties, resulting in an average coefficient of determination of 0.89 ± 0.04 with a slope of 0.93 ± 0.19 and a mean absolute error of 43 ± 10 µm when correlating in silico marker displacements with the ex vivo test. In conclusion, we validated a patient-specific computer model of an entire organ bone-implant system at the tissue-level at high resolution with excellent overall accuracy. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:954-962, 2018.