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OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique that allows for the non-invasive measurement of blood flow. Recent work has shown that utilizing longer wavelengths beyond the traditional NIR range provides a significant improvement to signal-to-noise ratio (SNR). However, current detectors both sensitive to longer wavelengths and suitable for clinical applications (InGaAs/InP SPADs) suffer from suboptimal afterpulsing and dark noise characteristics. To overcome these barriers, we introduce a cross correlation method to more accurately recover blood flow information using InGaAs/InP SPADs. METHODS: Two InGaAs/InP SPAD detectors were used for during in vitro and in vivo DCS measurements. Cross correlation of the photon streams from each detector was performed to calculate the correlation function. Detector operating parameters were varied to determine parameters which maximized measurement SNR. State-space modeling was performed to determine the detector characteristics at each operating point. RESULTS: Evaluation of detector characteristics was performed across the range of operating conditions. Modeling the effects of the detector noise on the correlation function provided a method to correct the distortion of the correlation curve, yielding accurate recovery of flow information as confirmed by a reference detector. CONCLUSION: Through a combination of cross-correlation of the signals from two detectors, model-based characterization of detector response, and optimization of detector operating parameters, the method allows for the accurate estimation of the true blood flow index. Significance: This work presents a method by which DCS can be performed at longer NIR wavelengths with existing detector technology, taking advantage of the increased SNR.

Label free and remote action potential detection in neurons can be of great importance in the neuroscience research field. This paper presents a novel label free imaging modality based on the detection of temporal vibrations of speckle patterns illuminating the sample. We demonstrated the feasibility of detecting action potentials originating from spontaneous and stimulated activity in cortical cell culture. The spatiotemporal vibrations of isolated cortical cells were extracted by illuminating the culture with a laser beam while the vibrations of the random back scattered secondary speckle patterns are captured by a camera. The postulated action potentials were estimated following correlation-based analysis on the captured vibrations, where the variance deviation of the signal from a Gaussian distribution is directly associated with the action potential events. The technique was validated in a series of experiments in which the optical signals were acquired concurrently with microelectrode array (MEA) recordings. Our results demonstrate the ability of detecting action potential events in mammalian cells remotely via extraction of acoustic vibrations.

Significance: The ability of diffuse correlation spectroscopy (DCS) to measure cerebral blood flow (CBF) in humans is hindered by the low signal-to-noise ratio (SNR) of the method. This limits the high acquisition rates needed to resolve dynamic flow changes and to optimally filter out large pulsatile oscillations and prevents the use of large source-detector separations (≥3 cm), which are needed to achieve adequate brain sensitivity in most adult subjects. Aim: To substantially improve SNR, we have built a DCS device that operates at 1064 nm and uses superconducting nanowire single-photon detectors (SNSPD). Approach: We compared the performances of the SNSPD-DCS in humans with respect to a typical DCS system operating at 850 nm and using silicon single-photon avalanche diode detectors. Results: At a 25-mm separation, we detected 13 ± 6 times more photons and achieved an SNR gain of 16 ± 8 on the forehead of 11 subjects using the SNSPD-DCS as compared to typical DCS. At this separation, the SNSPD-DCS is able to detect a clean pulsatile flow signal at 20 Hz in all subjects. With the SNSPD-DCS, we also performed measurements at 35 mm, showing a lower scalp sensitivity of 31 ± 6 % with respect to the 48 ± 8 % scalp sensitivity at 25 mm for both the 850 and 1064 nm systems. Furthermore, we demonstrated blood flow responses to breath holding and hyperventilation tasks. Conclusions: While current commercial SNSPDs are expensive, bulky, and loud, they may allow for more robust measures of non-invasive cerebral perfusion in an intensive care setting.

Recently, we developed a time-domain diffuse correlation spectroscopy (TD-DCS) method for neurovascular sensing with higher brain sensitivity. In this paper, laser pulse shaping was designed and demonstrated for TD-DCS at 1064 nm. A quantum superconducting nanowire single-photon detector (SNSPD) with high photon detection efficiency (PDE) and low jitter collects the back-scattered light from the brain. The presented approach is the first step towards scaling up a full fiber optic cap with 96 source channels and 192 custom-made single-photon detectors which will cover most of an adult head.

Diffuse correlation spectroscopy (DCS) is an established diffuse optical technique that uses the analysis of temporal speckle intensity fluctuations to measure blood flow in tissue. Recent advances in the field have seen the introduction of iDWS/iDCS, which have allowed for the use of conventional photodetectors to replace the single photon counting detectors required to measure the traditional, homodyne DCS signal. Here we detail a high framerate, highly parallel iDCS system at 1064 nm which allows for improved signal to noise ratio at extended source detector separations.

Diffuse correlation spectroscopy (DCS) is an established diffuse optical technique that uses the analysis of temporal speckle intensity fluctuations to measure blood flow in tissue. DCS cerebral blood flow measurements in clinical applications have shown promise, but measurements contain contamination of the signal from changes in superficial blood flow. Recent studies have shown that moving to wavelengths beyond the water absorption peak at 970 nm when making DCS measurements improves SNR and reduced influence of superficial flow. Here, we present a DCS system operating at 1064 nm utilizing two InGaAs SPADs to calculate the cross correlation to address detector non-idealities.

The ability of diffuse correlation spectroscopy (DCS) to measure tissue perfusion paves the way for monitoring cerebral blood flow (CBF) non-invasively. However, during measurements on human forehead, the measured blood flow index (BFi) is susceptible to contamination due to the blood flow in extracerebral tissue. Time domain DCS addresses this problem by selecting photons based on their travel time to obtain BFi at various depths. We have determined the gate start time(s) and width(s) that can lead to optimal sensitivity of BFi to CBF during actual measurements on human subjects through simulations. The simulated parameters were compared with measurement data.

Significance: Time domain diffuse correlation spectroscopy (TD-DCS) can offer increased sensitivity to cerebral hemodynamics and reduced contamination from extracerebral layers by differentiating photons based on their travel time in tissue. We have developed rigorous simulation and evaluation procedures to determine the optimal time gate parameters for monitoring cerebral perfusion considering instrumentation characteristics and realistic measurement noise. Aim: We simulate TD-DCS cerebral perfusion monitoring performance for different instrument response functions (IRFs) in the presence of realistic experimental noise and evaluate metrics of sensitivity to brain blood flow, signal-to-noise ratio (SNR), and ability to reject the influence of extracerebral blood flow across a variety of time gates to determine optimal operating parameters. Approach: Light propagation was modeled on an MRI-derived human head geometry using Monte Carlo simulations for 765- and 1064-nm excitation wavelengths. We use a virtual probe with a source–detector separation of 1 cm placed in the pre-frontal region. Performance metrics described above were evaluated to determine optimal time gate(s) for different IRFs. Validation of simulation noise estimates was done with experiments conducted on an intralipid-based liquid phantom. Results: We find that TD-DCS performance strongly depends on the system IRF. Among Gaussian pulse shapes, ∼300 ps pulse length appears to offer the best performance, at wide gates (500 ps and larger) with start times 400 and 600 ps after the peak of the TPSF at 765 and 1064 nm, respectively, for a 1-s integration time at photon detection rates seen experimentally (600 kcps at 765 nm and 4 Mcps at 1064 nm). Conclusions: Our work shows that optimal time gates satisfy competing requirements for sufficient sensitivity and sufficient SNR. The achievable performance is further impacted by system IRF with ∼300 ps quasi-Gaussian pulse obtained using electro-optic laser shaping providing the best results.

In this paper, we demonstrated a superconductive sensing-based system for cerebral blood flow monitoring via diffuse correlation spectroscopy at 1064nm. Findings show high brain sensitivity and fast monitoring using the presented system.

Significance: Diffuse correlation spectroscopy (DCS) is an established optical modality that enables noninvasive measurements of blood flow in deep tissue by quantifying the temporal light intensity fluctuations generated by dynamic scattering of moving red blood cells. Compared with near-infrared spectroscopy, DCS is hampered by a limited signal-to-noise ratio (SNR) due to the need to use small detection apertures to preserve speckle contrast. However, DCS is a dynamic light scattering technique and does not rely on hemoglobin contrast; thus, there are significant SNR advantages to using longer wavelengths (>1000 nm) for the DCS measurement due to a variety of biophysical and regulatory factors. Aim: We offer a quantitative assessment of the benefits and challenges of operating DCS at 1064 nm versus the typical 765 to 850 nm wavelength through simulations and experimental demonstrations. Approach: We evaluate the photon budget, depth sensitivity, and SNR for detecting blood flow changes using numerical simulations. We discuss continuous wave (CW) and time-domain (TD) DCS hardware considerations for 1064 nm operation. We report proof-of-concept measurements in tissue-like phantoms and healthy adult volunteers. Results: DCS at 1064 nm offers higher intrinsic sensitivity to deep tissue compared with DCS measurements at the typically used wavelength range (765 to 850 nm) due to increased photon counts and a slower autocorrelation decay. These advantages are explored using simulations and are demonstrated using phantom and in vivo measurements. We show the first high-speed (cardiac pulsation-resolved), high-SNR measurements at large source–detector separation (3 cm) for CW-DCS and late temporal gates (1 ns) for TD-DCS. Conclusions: DCS at 1064 nm offers a leap forward in the ability to monitor deep tissue blood flow and could be especially useful in increasing the reliability of cerebral blood flow monitoring in adults.

Vocal folds lesions are commonly diagnosed using an endoscopic-stroboscope. However, the stroboscopic picture of the vocal folds vibrations is subjectively and qualitatively evaluated by the clinician and, due to technical limitations, is unable to accurately distinguish between healthy and pathologic regions. In this paper, we propose two optical approaches for objectively sensing the vocal folds vibrations, using either external or internal laser illumination, based on temporal tracking of the reflected spatial distribution of secondary speckle patterns. The external configuration (the neck) is noninvasive and the internal configuration (the larynx) allows simultaneous extraction of data from multiple sites on the vocal folds. In this paper, we present measurements of healthy human subjects. Quantitative and precise measurements of vibration parameters of the vocal folds will enable a better understanding of hidden pathologies and optimize the diagnosis and treatment.

Light‐sheet fluorescence microscopy (LSFM) is a powerful technique that can provide high‐resolution images of biological samples. Therefore, this technique offers significant improvement for three‐dimensional (3D) imaging of living cells. However, producing high‐resolution 3D images of a single cell or biological tissues, normally requires high acquisition rate of focal planes, which means a large amount of sample sections. Consequently, it consumes a vast amount of processing time and memory, especially when studying real‐time processes inside living cells. We describe an approach to minimize data acquisition by interpolation between planes using a phase retrieval algorithm. We demonstrate this approach on LSFM data sets and show reconstruction of intermediate sections of the sparse samples. Since this method diminishes the required amount of acquisition focal planes, it also reduces acquisition time of samples as well. Our suggested method has proven to reconstruct unacquired intermediate planes from diluted data sets up to 10× fold. The reconstructed planes were found correlated to the original preacquired samples (control group) with correlation coefficient of up to 90%. Given the findings, this procedure appears to be a powerful method for inquiring and analyzing biological samples. Postprint

In this paper we propose a novel approach for remote speckle-based sensing of mechanical vibrations in the Hirudo medicinalis leech central nervous system (CNS) connective tissue. Using this method, spontaneous vibrations generated at the connective tissue following partial cut injury are continuously and remotely monitored. A laser beam illuminates the connective tissue and back scattered defocused patterns at the far field are captured by the camera. The spatialtemporal spontaneous vibrations of the connective are monitored by tracking the speckle spatial-temporal trajectory. After applying correlation-based analysis we were able to detect these vibrations of the connective tissue during recovery with respect to control measurements. This approach is the first step towards understanding the possible involvement of the tissue movements for the recovering process via mechanical vibrations sensing of the leech CNS connective tissue.

Radon gas was previously presented to be a good tool as a proxy for pre-seismic precursory before earthquakes, especially when the detector is deployed a few meters underground in regions of high seismic activity. In this paper, we present a fiber optic-based detector that can be deployed underground and assist in the measurement of radon gas temporal concentration variations. The sensitivity of the fiber-based sensor is enhanced due to Fabry-Perot resonator realized within the fiber. The sensing principle is related to the impact of the alpha particles released from the surrounding radon gas on the optical transmission parameters of the fiber. By incorporation of WDM filters along the fiber sensor, the dispersion of the radon's radiation damage along the deployed fiber can be allocated.

We present speckle and Michelson interference based photonic technique for performing depth measurement and elastography of a tissue. Photons from different depths of the tissue are separated by analyzing the flickering frequencies of collected speckles.

We will present how one can use the spatial-temporal analysis of secondary speckle patterns that are generated when laser light is back scattered from a tissue in order to measure the nano-vibrations (tilting associated vibrations) occurring in the tissue and in order to map its elastography. In addition to the fundamental nano-vibrations sensing capability, the proposed configuration allows by applying time multiplexing approach also to perform separation of photons coming from different depths of the tissue while externally stimulating the tissue via infra-sonic vibration. This yields a tomographic capability. The proposed configuration uses a modulated laser that allows combining a speckle pattern tracking method for surface tilting changes sensing with a Mach–Zehnder interferometer-based speckle patterns configuration to achieve z-axis detection (movement of the whole surface in the z direction). We will also show several methods for setup modulation to down convert high temporal frequencies to allow their sampling with a slow rate camera. As to be demonstrated in the experimental validation, the different elastographic layers (that were represented in our experiments by different concentrations of the agarose) have different temporal flickering and thereafter different temporal-spectral distribution which allows to extract their different elastographic characters.

A novel photonic method for remote monitoring of task-related hemodynamic changes in human brain activation is presented. Physiological processes associated with neural activity, such as nano-vibrations due to blood flow and tissue oxygenation in the brain, are detected by remote sensing of nano-acoustic vibrations using temporal spatial analysis of defocused self-interference random patterns. Temporal nanometric changes of the speckle pattern due to visual task-induced hemodynamic responses were tracked by this method. Reversing visual checkerboard stimulation alternated with rest epochs, and responsive signals were identified in occipital lobe using near-infrared spectroscopy. Temporal vibrations associated with these hemodynamic response functions were observed using three different approaches: (a) single spot illumination at active and control areas simultaneously, (b) subspots cross-correlation-based analysis, and (c) multiwavelength measurement using a magnitude-squared wavelet coherence function. Findings show remote sensing of task-specific neural activity in the human brain.

In this Perspective Letter, we discuss the field of remote photonic bio-sensing and diagnosis while focusing on sensing involving spatial analysis of temporally varied defocused secondary speckle patterns. Collecting secondary speckle patterns that were back-reflected from an inspected tissue while properly defocusing the imaging lens allows us to measure nano-vibrations occurring in the tissue. The nano-vibration signal can serve as the common denominator for simultaneous estimation of many bio-medical parameters related to vital bio-signs, hematology, and hemodynamics. This can provide a powerful tool for comprehensive medical diagnosis.

This paper is an initial proof of concept for an optical speckled-based method for the evaluation of facial nerve paralysis. Differences between the affected and the healthy sides of the face were measured in patients with Bell's palsy—a peripheral facial nerve paralysis. The patients’ faces were illuminated with two symmetrical spots on their nasolabial folds and the reflected speckle patterns were analyzed. Muscle activity was evaluated by muscle tone contraction-release motion inducing associated skin tilting movements. The skin movements were imaged with a defocused lens, which enables extraction of the speckle pattern's time changing trajectory. We found an asymmetry ratio expression that may be the key for the estimation of the degeneration level in Bell's palsy.

A method for fast non-scanning remote photoacoustic imaging is presented and experimentally demonstrated. The approach is based on speckle contrast measurement, proceeding the previously developed method for speckle contrast based photoacoustic detection. This previously developed method is now presented without the need for raster scanning of the sample, an advantage rarely found in optical photoacoustic detection, and offers 50 times faster as well as a simpler remote photoacoustic scheme in respect to interferometric available solutions.

A non-contact optical method based on laser speckle contrast analysis in IR for monitoring of blood pulsation is compared to remote PPG. Suggested method show superiority at anatomic sites with week pulsation.

An optical approach to the extraction and separation of remote vibration sources has recently been proposed. The technique has previously been applied successfully to biomedical measurements including pulse pressure, heart rate, blood glucose and alcohol concentrations, and intraocular pressure. In this paper, we review this optical sensing technology and demonstrate its ability to monitor three additional biomedical indicators, breathing, blood oximetry, and blood coagulation, as well as its ability to simultaneously monitor indicators that were previously only monitored separately. The proposed compact and potentially low-cost biomedical sensor can be highly beneficial given the global healthcare challenges, especially in the developing countries.

Brillouin scattering is a nonlinear effect in optical fibers which can be used for temperature or strain sensing. For read-out and analysis of the scattered signal, spectrum-analyzers with a very high resolution or complex detection systems are currently needed. In this work, a new detection modality for radial acoustic modes in optical fibers based on speckle-sensing is presented.

Middle ear effusion (MEE) is related to a group of inflammatory diseases of the middle ear. There are two main groups of otitis media (OM): The first group refers to acute OM (AOM), typically expressed by pain and elevated temperature of an acute onset, related to an infection of the middle ear that is caused by known pathogens (viruses and bacteriae). The second group, refers to OM with effusion (OME), has a rather benign course and is mainly presented with hearing loss. These two disorders share a significant impact upon public health and both demand appropriate diagnosis and specific treatment [1].

In this paper we present the usage of photonic remote laser based device for sensing nano-vibrations for detection of muscle contraction and fatigue, eye movements and in-vivo estimation of glucose concentration. The same concept is also used to realize a remote optical stethoscope. The advantage of doing the measurements from a distance is in preventing passage of infections as in the case of optical stethoscope or in the capability to monitor e.g. sleep quality without disturbing the patient. The remote monitoring of glucose concentration in the blood stream and the capability to perform opto-myography for the Messer muscles (chewing) is very useful for nutrition and weight control. The optical configuration for sensing the nano-vibrations is based upon analyzing the statistics of the secondary speckle patterns reflected from various tissues along the body of the subjects. Experimental results present the preliminary capability of the proposed configuration for the above mentioned applications.

An optical approach to determine the hydration level in human skin is presented. The approach is based on temporal tracking of back-reflected secondary speckle patterns generated while illuminating the tested area with a laser and applying periodic vibrations to the surface via a controlled vibration source (CVS). This approach has already been tested successfully for other biomedical parameters such as sensing vital signs, hematology and hemodynamic processes in the body. In this paper we examine and adjust this optical technique with the aim of measuring human skin moisture. We compare the suitability and accuracy of our optical method to the commercially available device for skin moisture measurements, the Corneometer CM 825 (by Courage + Khazaka, Cologne, Germany). Preliminary experiments showing the method's suitability for hydration measurements are presented, may lead to more accurate results that may upgrade the control of the cosmetic industry as well as identifying symptoms of moisture-related skin diseases.

A novel method for non-contact and continuous detection of photoacoustic signals is presented and experimentally demonstrated. The approach is based on analysis of the contrast of time-varying speckle patterns, and suggests a more robust alternative in respect to interferometric and refractometric available solutions.

The implementation of augmentative alternative communication optical device for ALS speech problem is presented. The sensor is based on temporal tracking of back-reflected secondary speckle patterns generated when illuminating an eyelid with a laser.

The implementation of a simple, inexpensive optical device for remote fingerprint identification is presented. The sensor is based on temporal tracking of back-reflected secondary speckle patterns generated while illuminating a finger with a laser.

In this paper we propose a modulated laser system combining a speckle pattern tracking method for surface tilting changes sensing with an interferometer for surface z-axis changes sensing at the same scan time.

In this paper we aim to experimentally verify a speckle based technique for non-contact measurement of glucose concentration in blood stream while the vision for the final device aims to contain a single wristwatch-style device containing an AC (alternating) electro-magnet generated by a solenoid, a laser and a camera. The experiments presented in work are performed in-vitro in order to verify the effects that are responsible for the operation principle. When a glucose substance is inserted into a solenoid generating an alternating magnetic field it exhibits Faraday rotation which affects the temporal changes of the secondary speckle patterns distribution. The temporal frequency resulting from the AC magnetic field was found to have a lock-in amplification role which increased the observability of the relatively small magneto-optic effect. Experimental results to support the proposed concept are presented.

In this paper we present a novel approach of realizing a safe, simple, and inexpensive sensor applicable to bone fractures and pigmented lesions detection. The approach is based on temporal tracking of back-reflected secondary speckle pattern generated while illuminating the affected area with a laser and applying periodic pressure to the surface via a controlled vibration. The use of such a concept was already demonstrated for non-contact monitoring of various bio-medical parameters such as heart rate, blood pulse pressure, concentration of alcohol and glucose in the blood stream and intraocular pressure. The presented technique is a safe and effective method of detecting bone fractures in populations at risk. When applied to pigmented lesions, the technique is superior to visual examination in avoiding many false positives and resultant unnecessary biopsies. Applying a series of different vibration frequencies at the examined tissue and analyzing the 2-D speckle pattern trajectory in response to the applied periodic pressure creates a unique signature for each and different pigmented lesion. Analyzing these signatures is the first step toward detection of malignant melanoma. In this paper we present preliminary experiments that show the validity of the developed sensor for both applications: the detection of damaged bones as well as the classification of pigmented lesions.

Continuous noninvasive measurement of intraocular pressure (IOP) is an important tool in the evaluation process for glaucoma. We present a methodology enabling high-precision, noncontact, reproducible, and continuous monitoring of IOP based on the value of the damping factor of transitional oscillations obtained at the surface of the eye after terminating its stimulation by a sound wave. The proposed configuration includes projection of a laser beam and usage of a fast camera for analyzing the temporal-spatial variations of the speckle patterns backscattered from the iris or the sclera following the above-mentioned sound waves external stimulation. The methodology was tested on an artificial eye and a carp fish eye under varying pressure as well as on human eyes.

Otitis Media (OM) is related to a group of inflammatory diseases of the middle ear (ME) commonly encountered, worldwide. A method based on a simple device, which can be used by medical staff and non-experts to detect OM is presented. The method is based on detection of tympanic membrane (TM) vibrations. A laser beam is pointed on an infra-sonic stimulated TM with fast camera capturing the back scattered secondary speckle patterns. A camera enables inspection of the frequency and amplitude of the changes in TM characteristics obtained by analysis of the spatial-temporal statistics of the speckle patterns. The results may provide information that express ME effusion.