Real-time ultrasound sensing with a mode-optimized photonic crystal slab.

Integrated photonic sensors can provide large scale, flexible detection schemes. Photonic crystal slabs (PCSs) offer a miniaturized platform for wideband, sensitive ultrasound detection by exploiting the photoelastic effect in water. However, poor modal overlap with the sensing medium and non-negligible absorption loss of the aqueous medium have previously limited PCS sensor performance. In this study, we detail the development and optimization of a PCS-based acoustic sensor by adding to it a low-loss high-index polymer cladding layer. Exploiting a mode-optimized TM-like optical resonance present in a PCS, with high bulk index sensitivity (>600nm/RIU) and quality factor Q (>8000), we demonstrate real-time ultrasound sensing at a noise equivalent pressure of 170 Pa (1.9Pa/Hz). The PCS sensor is backside-coupled to an optical fiber, which, along with its intensity-based ultrasound-sensing architecture, will allow us to scale up easily to a 2D array. This work paves the way to a sensitive compact ultrasound detector for photoacoustic-based diagnostics and monitoring of tissue.

Refractive-index-based ultrasound sensing with photonic crystal slabs.

We demonstrate ultrasound detection with 500-µm-diameter photonic-crystal slab (PCS) sensors fabricated from CMOS-compatible technology. An ultrasound signal impinging a PCS sensor causes a local modulation of the refractive index (RI) of the medium (water) in which the PCS is immersed, resulting in a periodic spectral shift of the optical resonance of the PCS. The acoustic sensitivity is found to scale with the index sensitivity S and quality factor Q. A noise equivalent pressure (NEP) of 650 Pa with averaging (7.4 Pa/Hz) and relative wavelength shifts of up to 4.3×10-5 MPa-1 are measured. The frequency response of the sensors is observed to be flat from 1 to 20 MHz, with the range limited only by our measurement apparatus.

Tailoring of spectral response and spatial field distribution with corrugated photonic crystal slab.

We report a new physical mechanism for simultaneous tuning of quality factors, spectral responses, and field distributions in photonic crystal slabs through removal of polarization mode degeneracy using a lattice of elliptical nano-holes. The quality factors in these structures can become higher than those obtained with much smaller circular nano-holes. Furthermore, the modes can be superimposed by either rotating or morphing the elliptical nano-holes into a corrugated grating. These findings will enable improved radiation-matter interaction in optical, microwave, and THZ frequencies along with enhanced opto-acoustic coupling.

Spreading depolarization suppression from inter-astrocytic gap junction blockade assessed with multimodal imaging and a novel wavefront detection scheme.

Spreading depolarizations (SDs) are an enigmatic and ubiquitous co-morbidity of neural dysfunction. SDs are propagating waves of local field depolarization and increased extracellular potassium. They increase the metabolic demand on brain tissue, resulting in changes in tissue blood flow, and are associated with adverse neurological consequences including stroke, epilepsy, neurotrauma, and migraine. Their occurrence is associated with poor patient prognosis through mechanisms which are only partially understood. Here we show in vivo that two (structurally dissimilar) drugs, which suppress astroglial gap junctional communication, can acutely suppress SDs. We found that mefloquine hydrochloride (MQH), administered IP, slowed the propagation of the SD potassium waveform and intermittently led to its suppression. The hemodynamic response was similarly delayed and intermittently suppressed. Furthermore, in instances where SD led to transient tissue swelling, MQH reduced observable tissue displacement. Administration of meclofenamic acid (MFA) IP was found to reduce blood flow, both proximal and distal, to the site of SD induction, preceding a large reduction in the amplitude of the SD-associated potassium wave. We introduce a novel image processing scheme for SD wavefront localization under low-contrast imaging conditions permitting full-field wavefront velocity mapping and wavefront parametrization. We found that MQH administration delayed SD wavefront's optical correlates. These two clinically used drugs, both gap junctional blockers found to distinctly suppress SDs, may be of therapeutic benefit in the various brain disorders associated with recurrent SDs.

Enhanced detection limit by dark mode perturbation in 2D photonic crystal slab refractive index sensors.

We demonstrate for the first time a 300nm thick, 300µm × 300µm 2D dielectric photonic crystal slab membrane with a quality factor of 10,600 by coupling light to slightly perturbed dark modes through alternating nano-hole sizes. The newly created fundamental guided resonances greatly reduce nano-fabrication accuracy requirements. Moreover, we created a new layer architecture resulting in electric field enhancement at the interface between the slab and sensing regions, and spectral sensitivity of >800 nm/RIU, that is, >0.8 of the single-mode theoretical upper limit of spectral sensitivity.

Rapid multiexposure in vivo brain imaging system using vertical cavity surface emitting lasers as a light source.

We demonstrate an imaging technique implementing vertical cavity lasers with extremely low transient times for a greatly simplified realization of a multiexposure laser speckle contrast imaging system. Data from multiexposure laser speckle imaging was observed to more closely agree with absolute velocity measurements using time of flight technique, when compared to long-exposure laser speckle imaging. Furthermore, additional depth information of the vasculature morphology was inferred by accounting for the change in the static scattering from tissue above vessels with respect to the total scattering from blood flow and tissue.

Exploring exercise adherence and quality of life among veteran, novice, and dropout trainees.

Introduction: The purpose of this study was to identify and reveal the different contexts, variables, and factors that may influence adherence to physical activity among veteran, novice, and dropout trainees, such as the frequency of the weekly training units, the trainees preferred type of exercise, the purpose of the physical activity, and the relationship between support and supervision by fitness instructors and professionals. This study also examined the relationships between trainees, seniority and the strength of the habit and adherence to physical activity, the effects of personal variables such as age and gender on adherence to physical activity, and how the seniority and adherence of trainees may affect their quality of life. Methods: A total of 460 participants drawn from the broader Israeli exercise community, which encompasses a diverse range of individuals within the general adult population, were engaged in this study. These participants included seasoned exercisers, individuals who had recently initiated exercise routines, and those who had previously engaged in physical activity. Each participant completed a comprehensive set of questionnaires, including the Self-Report Habit Index, the Exercise Adherence Rating Scale, and the World Health Organization (WHO) Quality of Life Scale. In addition to the questionnaire responses, demographic data and inquiries concerning their physical activity were also collected. Results: The results show that the average frequency of the weekly training units of veteran trainees was significantly higher than that of novice trainees: 3.95 and 2.93, respectively (p < 0.0001). We found no significant differences between novice and veteran trainees regarding their training goal preferences (p = 0.07). Veteran trainees who had been in training for more than a year appeared to have higher self-efficacy since 31.16% reported receiving no supervision compared to 16.67% among novice trainees. In addition, people over 45 appear to have more health-related goals compared to their younger counterparts (p < 0.001). The quality of life scores of the trainees was related to their seniority in physical training, but only by a small magnitude (R2 = 0.06), p < .001). Those who trained in resistance training showed the greatest rate of adherence in relation to flexibility and aerobic training (p < 0.001), and women preferred more body toning and had more weight loss goals than men (p < 0.001). Discussion: The results indicate that there are central and important factors that may affect adherence to physical activity, and that all these aspects must be taken into account when planning a training program or when there is a desire to maintain or increase adherence to physical activity. The research findings indicate that the main factors that can influence adherence to physical activity are identifying and increasing the trainee's self-efficacy, maintaining weekly training units with sufficient frequency to form a habit and incorporating resistance training into the training regime, as resistance training has shown high levels of adherence. Moreover, it seems that people with different degrees of experience in physical training have distinct and varied training goals, and there is no one goal that fits all. In addition, specific factors such as age and gender must also be taken into account, because the age and gender of the trainees may significantly affect the goals of physical training.

Progressive compressive imaging from Radon projections.

In this work we propose a unique sampling scheme of Radon Projections and a non-linear reconstruction algorithm based on compressive sensing (CS) theory to implement a progressive compressive sampling imaging system. The progressive sampling scheme offers online control of the tradeoff between the compression and the quality of reconstruction. It avoids the need of a priori knowledge of the object sparsity that is usually required for CS design. In addition, the progressive data acquisition enables straightforward application of ordered-subsets algorithms which overcome computational constraints associated with the reconstruction of very large images. We present, to the best of our knowledge for the first time, a compressive imaging implementation of megapixel size images with a compression ratio of 20:1.

Optical compressive change and motion detection.

Localization information of moving and changing objects, as commonly extracted from video sequences, is typically very sparse with respect to the full data frames, thus fulfilling one of the basic conditions of compressive sensing theory. Motivated by this observation, we developed an optical compressive change and motion-sensing technique that detects the location of moving objects by using a significantly fewer samples than conventionally taken. We present examples of motion detection and motion tracking with over two orders of magnitude fewer samples than required with conventional systems.

Multi-modality optical neural imaging using coherence control of VCSELs.

Neural optical imaging can evaluate cortical hemodynamic fluctuations which reflect neural activity and disease state. We evaluate the use of vertical-cavity surface-emitting lasers (VCSELs) as illumination source for simultaneous imaging of blood flow and tissue oxygenation dynamics ex vivo and in vivo and demonstrate optical imaging of blood flow changes and oxygenation changes in response to induced ischemia. Using VCSELs we show a rapid switching from a single-mode to a special multi-mode rapid current sweep operation and noise values reduced to within a factor of 40% compared to non-coherent LED illumination. These VCSELs are promising for long-term portable continuous monitoring of brain dynamics in freely moving animals.

Sensitivity enhancement in photonic crystal slab biosensors.

Refractive index sensitivity of guided resonances in photonic crystal slabs is analyzed. We show that modal properties of guided resonances strongly affect spectral sensitivity and quality factors, resulting in substantial enhancement of refractive index sensitivity. A three-fold spectral sensitivity enhancement is demonstrated for suspended slab designs, in contrast to designs with a slab resting over a substrate. Spectral sensitivity values are additionally shown to be unaffected by quality factor reductions, which are common to fabricated photonic crystal nano-structures. Finally, we determine that proper selection of photonic crystal slab design parameters permits biosensing of a wide range of analytes, including proteins, antigens, and cells. These photonic crystals are compatible with large-area biosensor designs, permitting direct access to externally incident optical beams in a microfluidic device.

Implantable semiconductor biosensor for continuous in vivo sensing of far-red fluorescent molecules.

We have fabricated miniature implantable fluorescence sensors for continuous fluorescence sensing applications in living subjects. These monolithically integrated GaAs-based sensors incorporate a 675 nm vertical-cavity surface-emitting laser (VCSEL), a GaAs PIN photodiode, and a fluorescence emission filter. We demonstrate high detection sensitivity for Cy5.5 far-red dye (50 nanoMolar) in living tissue, limited by the intrinsic background autofluorescence. These low cost, sensitive and scalable sensors are promising for long-term continuous monitoring of molecular dynamics for biomedical studies in freely moving animals.

Comparative Quality Control of Titanium Alloy Ti-6Al-4V, 17-4 PH Stainless Steel, and Aluminum Alloy 4047 Either Manufactured or Repaired by Laser Engineered Net Shaping (LENS).

Additive manufacturing attracts much interest for manufacturing and repair of structural parts for the aerospace industry. This paper presents comparative characterization of aircraft items made of Al 4047 alloy, Ti-6Al-4V alloy, and 17-4 precipitation hardened (PH) (AISI 630) stainless steel, either manufactured or repaired by laser engineered net shaping (LENS). Chemical analysis, density, and surface roughness measurements, X-ray micro-computed tomography (µ-CT) analysis, metallography, and micro-hardness testing were conducted. In all three materials, microstructures typical of rapid solidification were observed, along with high density, chemical composition, and hardness comparable to those of the counterpart wrought alloys (even in hard condition). High standard deviation in hardness values, anisotropic geometrical distortion, and overbuild at top edges were observed. The detected defects included partially melted and unmelted powder particles, porosity, and interlayer lack of fusion, in particular at the interface between the substrate plate and the build. There was a fairly good match between the density values measured by µ-CT and those measured by the Archimedes method; there was also good correlation between the type of defects detected by both techniques. Surface roughness, density of partially melted powder particles, and the content of bulk defects were significantly higher in Al 4047 than in 17-4 PH stainless steel and Ti-6Al-4V alloy. Optical gaging can be used reliably for surface roughness measurements. The implications of these findings are discussed.

Brain mapping of patients with lung cancer and controls: inquiry into tumor-to-brain communication.

UNLABELLED: Recent converging evidence suggests that the brain may receive stimuli and possibly modulate tumor progression via the vagus nerve. The present study aimed to compare brain metabolism in patients with and without lung cancer and to assess if significant differences exist in regions associated with the vagus nerve. METHODS: Eighteen patients with lung malignancy and 19 controls underwent (18)F-FDG PET of the brain. Brain metabolism was compared using statistical parametric mapping. RESULTS: Patients with lung malignancy showed a statistically significantly higher right cerebellar metabolism. CONCLUSION: This finding may be related to the role of the cerebellum in immune regulation, because of its proximity to the nucleus tractus solitarius innervated by the vagus and its connections with the hypothalamus. This higher metabolism in the right cerebellum may reflect an attempt to reinstate homeostasis in functions such as respiration and immunity pertinent to lung malignancy.

Mechanical properties of Bio-Ferrography isolated cancerous cells studied by atomic force microscopy.

Detecting the presence of circulating tumor cells (CTCs) in peripheral blood can be useful for monitoring treatment in patients, metastasis prognosis, and even early detection. The epidermal growth factor receptor (EGFR) is overexpressed in carcinoma, e.g. in colorectal cancer. Here, we use atomic force microscopy (AFM) force spectroscopy to study the mechanical properties of A431 cells, which simulate EGFR-overexpressing epithelial CTCs and were magnetically isolated by Bio-Ferrography (BF). BF is found useful in isolating individual cancerous cells for mechanical testing, thus avoiding cell-cell interactions. Different stages in the pre-isolation sample preparation steps (namely, cell fixation, PLL coating of the glass substrate, and immunomagnetic labeling) are found to affect the estimated Young's modulus. The BF magnetic isolation step itself does not change the elasticity of the captured cells in comparison to the pre-isolated microbeads-bound cells. The reported increase in the estimated Young's modulus between BF-isolated target cells and fixed cells that are not bound to magnetic microbeads can be used as a quantitative mechanical indicator for objective detection of CTCs. Furthermore, we report a 2.8-fold increase in the adhesion force between the AFM tip and the BF-isolated cells compared to the pre-isolated magnetic microbead-bound A431 fixed cells. This adhesion force correlation could potentially serve as an additional quantitative mechanical indicator for distinguishing between the target and background cells, without the use of cell staining assay and subjective analysis by an expert pathologist. This study demonstrates the powerful combination of the highly sensitive cell isolation by BF and the subsequent analysis of mechanical properties of individual captured cancerous cells by AFM. This combination has potential use in cancer research.

Data compression and improved registration for laser speckle contrast imaging of rodent brains.

Single-frame blood flow maps from laser speckle contrast imaging (LSCI) contain high spatiotemporal variation that obscures high spatial-frequency vascular features, making precise image registration for signal amplification challenging. In this work, novel bivariate standardized moment filters (BSMFs) were used to provide stable measures of vessel edge location, permitting more robust LSCI registration. Relatedly, BSMFs enabled the stable reconstruction of vessel edges from sparsely distributed blood flow map outliers, which were found to retain most of the temporal dynamics. Consequently, data discarding and BSMF-based reconstruction enable efficient real-time quantitative LSCI data compression. Smaller LSCI-kernels produced log-normal blood flow distributions, enhancing sparse-to-dense inference.

Continuous multi-modality brain imaging reveals modified neurovascular seizure response after intervention.

We developed a multi-modal brain imaging system to investigate the relationship between blood flow, blood oxygenation/volume, intracellular calcium and electrographic activity during acute seizure-like events (SLEs), both before and after pharmacological intervention. Rising blood volume was highly specific to SLE-onset whereas blood flow was more correlated with all eletrographic activity. Intracellular calcium spiked between SLEs and at SLE-onset with oscillation during SLEs. Modified neurovascular and ionic SLE responses were observed after intervention and the interval between SLEs became shorter and more inconsistent. Comparison of artery and vein pulsatile flow suggest proximal interference and greater vascular leakage prior to intervention.

Heart rate analysis by sparse representation for acute pain detection.

Objective pain assessment methods pose an advantage over the currently used subjective pain rating tools. Advanced signal processing methodologies, including the wavelet transform (WT) and the orthogonal matching pursuit algorithm (OMP), were developed in the past two decades. The aim of this study was to apply and compare these time-specific methods to heart rate samples of healthy subjects for acute pain detection. Fifteen adult volunteers participated in a study conducted in the pain clinic at a single center. Each subject's heart rate was sampled for 5-min baseline, followed by a cold pressor test (CPT). Analysis was done by the WT and the OMP algorithm with a Fourier/Wavelet dictionary separately. Data from 11 subjects were analyzed. Compared to baseline, The WT analysis showed a significant coefficients' density increase during the pain incline period (p < 0.01) and the entire CPT (p < 0.01), with significantly higher coefficient amplitudes. The OMP analysis showed a significant wavelet coefficients' density increase during pain incline and decline periods (p < 0.01, p < 0.05) and the entire CPT (p < 0.001), with suggestive higher amplitudes. Comparison of both methods showed that during the baseline there was a significant reduction in wavelet coefficient density using the OMP algorithm (p < 0.001). Analysis by the two-way ANOVA with repeated measures showed a significant proportional increase in wavelet coefficients during the incline period and the entire CPT using the OMP algorithm (p < 0.01). Both methods provided accurate and non-delayed detection of pain events. Statistical analysis proved the OMP to be by far more specific allowing the Fourier coefficients to represent the signal's basic harmonics and the wavelet coefficients to focus on the time-specific painful event. This is an initial study using OMP for pain detection; further studies need to prove the efficiency of this system in different settings.

Imaging brain activity during seizures in freely behaving rats using a miniature multi-modal imaging system.

We report on a miniature label-free imaging system for monitoring brain blood flow and blood oxygenation changes in awake, freely behaving rats. The device, weighing 15 grams, enables imaging in a ∼ 2 × 2 mm field of view with 4.4 µm lateral resolution and 1 - 8 Hz temporal sampling rate. The imaging is performed through a chronically-implanted cranial window that remains optically clear between 2 to > 6 weeks after the craniotomy. This imaging method is well suited for longitudinal studies of chronic models of brain diseases and disorders. In this work, it is applied to monitoring neurovascular coupling during drug-induced absence-like seizures 6 weeks following the craniotomy.

Reducing misfocus-related motion artefacts in laser speckle contrast imaging.

Laser Speckle Contrast Imaging (LSCI) is a flexible, easy-to-implement technique for measuring blood flow speeds in-vivo. In order to obtain reliable quantitative data from LSCI the object must remain in the focal plane of the imaging system for the duration of the measurement session. However, since LSCI suffers from inherent frame-to-frame noise, it often requires a moving average filter to produce quantitative results. This frame-to-frame noise also makes the implementation of rapid autofocus system challenging. In this work, we demonstrate an autofocus method and system based on a novel measure of misfocus which serves as an accurate and noise-robust feedback mechanism. This measure of misfocus is shown to enable the localization of best focus with sub-depth-of-field sensitivity, yielding more accurate estimates of blood flow speeds and blood vessel diameters.