Telepathology and Optical Biopsy

The ability to obtain information about the structure of tissue without taking a sample for pathology has opened the way for new diagnostic techniques. The present paper reviews all currently available techniques capable of producing an optical biopsy, with or without morphological images. Most of these techniques are carried out by physicians who are not specialized in pathology and therefore not trained to interpret the results as a pathologist would. In these cases, the use of telepathology or distant consultation techniques is essential

Review of recent advances in frequency-domain near-infrared spectroscopy technologies [Invited]

Over the past several decades, near-infrared spectroscopy (NIRS) has become a popular research and clinical tool for non-invasively measuring the oxygenation of biological tissues, with particular emphasis on applications to the human brain. In most cases, NIRS studies are performed using continuous-wave NIRS (CW-NIRS), which can only provide information on relative changes in chromophore concentrations, such as oxygenated and deoxygenated hemoglobin, as well as estimates of tissue oxygen saturation. Another type of NIRS known as frequency-domain NIRS (FD-NIRS) has significant advantages: it can directly measure optical pathlength and thus quantify the scattering and absorption coefficients of sampled tissues and provide direct measurements of absolute chromophore concentrations. This review describes the current status of FD-NIRS technologies, their performance, their advantages, and their limitations as compared to other NIRS methods. Significant landmarks of technological progress include the development of both benchtop and portable/wearable FD-NIRS technologies, sensitive front-end photonic components, and high-frequency phase measurements. Clinical applications of FD-NIRS technologies are discussed to provide context on current applications and needed areas of improvement. The review concludes by providing a roadmap toward the next generation of fully wearable, low-cost FD-NIRS systems

Kernel Flow:a high channel count scalable time-domain functional near-infrared spectroscopy system

Significance: Time-domain functional near-infrared spectroscopy (TD-fNIRS) has been considered as the gold standard of noninvasive optical brain imaging devices. However, due to the high cost, complexity, and large form factor, it has not been as widely adopted as continuous wave NIRS systems. Aim: Kernel Flow is a TD-fNIRS system that has been designed to break through these limitations by maintaining the performance of a research grade TD-fNIRS system while integrating all of the components into a small modular device. Approach: The Kernel Flow modules are built around miniaturized laser drivers, custom integrated circuits, and specialized detectors. The modules can be assembled into a system with dense channel coverage over the entire head. Results: We show performance similar to benchtop systems with our miniaturized device as characterized by standardized tissue and optical phantom protocols for TD-fNIRS and human neuroscience results. Conclusions: The miniaturized design of the Kernel Flow system allows for broader applications of TD-fNIRS.</p

Towards next generation time-domain diffuse optics devices

Diffuse Optics is growing in terms of applications ranging from e.g. oximetry, to mammography, molecular imaging, quality assessment of food and pharmaceuticals, wood optics, physics of random media. Time-domain (TD) approaches, although appealing in terms of quantitation and depth sensibility, are presently limited to large fiber-based systems, with limited number of source-detector pairs. We present a miniaturized TD source-detector probe embedding integrated laser sources and single-photon detectors. Some electronics are still external (e.g. power supply, pulse generators, timing electronics), yet full integration on-board using already proven technologies is feasible. The novel devices were successfully validated on heterogeneous phantoms showing performances comparable to large state-of-the-art TD rack-based systems. With an investigation based on simulations we provide numerical evidence that the possibility to stack many TD compact source-detector pairs in a dense, null source-detector distance arrangement could yield on the brain cortex about 1 decade higher contrast as compared to a continuous wave (CW) approach. Further, a 3-fold increase in the maximum depth (down to 6 cm) is estimated, opening accessibility to new organs such as the lung or the heart. Finally, these new technologies show the way towards compact and wearable TD probes with orders of magnitude reduction in size and cost, for a widespread use of TD devices in real life

A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination.

Rationale: Intraoperative visualization in small surgical cavities and hard-to-access areas are essential requirements for modern, minimally invasive surgeries and demand significant miniaturization. However, current optical imagers require multiple hard-to-miniaturize components including lenses, filters and optical fibers. These components restrict both the form-factor and maneuverability of these imagers, and imagers largely remain stand-alone devices with centimeter-scale dimensions. Methods: We have engineered INSITE (Immunotargeted Nanoparticle Single-Chip Imaging Technology), which integrates the unique optical properties of lanthanide-based alloyed upconverting nanoparticles (aUCNPs) with the time-resolved imaging of a 25-micron thin CMOS-based (complementary metal oxide semiconductor) imager. We have synthesized core/shell aUCNPs of different compositions and imaged their visible emission with INSITE under either NIR-I and NIR-II photoexcitation. We characterized aUCNP imaging with INSITE across both varying aUCNP composition and 980 nm and 1550 nm excitation wavelengths. To demonstrate clinical experimental validity, we also conducted an intratumoral injection into LNCaP prostate tumors in a male nude mouse that was subsequently excised and imaged with INSITE. Results: Under the low illumination fluences compatible with live animal imaging, we measure aUCNP radiative lifetimes of 600 μs - 1.3 ms, which provides strong signal for time-resolved INSITE imaging. Core/shell NaEr0.6Yb0.4F4 aUCNPs show the highest INSITE signal when illuminated at either 980 nm or 1550 nm, with signal from NIR-I excitation about an order of magnitude brighter than from NIR-II excitation. The 55 μm spatial resolution achievable with this approach is demonstrated through imaging of aUCNPs in PDMS (polydimethylsiloxane) micro-wells, showing resolution of micrometer-scale targets with single-pixel precision. INSITE imaging of intratumoral NaEr0.8Yb0.2F4 aUCNPs shows a signal-to-background ratio of 9, limited only by photodiode dark current and electronic noise. Conclusion: This work demonstrates INSITE imaging of aUCNPs in tumors, achieving an imaging platform that is thinned to just a 25 μm-thin, planar form-factor, with both NIR-I and NIR-II excitation. Based on a highly paralleled array structure INSITE is scalable, enabling direct coupling with a wide array of surgical and robotic tools for seamless integration with tissue actuation, resection or ablation

Fiber-coupled Antennas for Ultrafast Coherent Terahertz Spectroscopy in Low Temperatures and High Magnetic Fields

For the purposes of measuring the high-frequency complex conductivity of correlated-electron materials at low temperatures and high magnetic fields, a method is introduced for performing coherent time-domain terahertz spectroscopy directly in the cryogenic bore of existing dc and pulsed magnets. Miniature fiber-coupled THz emitters and receivers are constructed and are demonstrated to work down to 1.5 Kelvin and up to 17 Tesla, for eventual use in higher-field magnets. Maintaining the sub-micron alignment between fiber and antenna during thermal cycling, obtaining ultrafast (${<200}$~fs) optical gating pulses at the end of long optical fibers, and designing highly efficient devices that work well with low-power optical gating pulses constitute the major technical challenges of this project. Data on a YBCO superconducting thin film and a high mobility 2D electron gas is shown.Comment: 8 pages, 9 figure