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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.

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. 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.

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.

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.

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.

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.

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.

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.

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.

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.

The growing interest in photoacoustic imaging using nanoparticles stems from the improved penetration depth and resolution. Such methods require pulsed laser in order to generate acoustic signal in the right frequency. In this paper we design special nanostructure which blinks under CW illumination and can be used for generation of acoustic signals

Over the last few years, there is a growing interest in photoacoustic imaging using nanoparticles techniques due to the improved penetration depth and resolution. Working with such nanoparticles usually requires pulsed laser illumination to generate an acoustic signal in the right frequencies. However, these pulsed lasers are considered expensive and complicated with respect to continuous-wave (CW) illumination. We design and simulate a special nanostructure with overall dimensions of 190×50× (26–34) nm, which blinks with fast temporal periodicity of 20 to 40 ns, under CW illumination and can be used for the generation of acoustic signals. This blinking is done using the enhanced optical absorption of metallic nanoparticles due to localized surface plasmon resonance (SPR) and the thermal expansion to generate heating–cooling cycles of the nanostructure. The CW laser wavelength is adapted to the localized SPR of the metallic nanostructure at the NIR region, which provides maximum penetration depth of light into biological tissues.

The ability to extract different bio-medical parameters from one single wristwatch device can be very applicable. The wearable device that is presented in this paper is based on two optical approaches. The first is the extraction and separation of remote vibration sources and the second is the rotation of linearly polarized light by certain materials exposed to magnetic fields. The technique is based on tracking of temporal changes of reflected secondary speckles produced in the wrist when being illuminated by a laser beam. Change in skin’s temporal vibration profile together with change in the magnetic medium that is generated by time varied glucose concentration caused these temporal changes. In this paper we present experimental tests which are the first step towards an in vivo noncontact device for detection of glucose concentration in blood. The paper also shows very preliminary results for qualitative capability for indication of dehydration.

An optical approach for remote extraction of vibrations has recently been proposed. We demonstrate the method's ability to continuously monitor three biomedical indicators: blood oximetry, blood coagulation and dehydration of the body.

We present the first steps of a device suitable for characterization of complex 3D micro-structures. This method is based on an optical approach allowing extraction and separation of high frequency ultrasonic sound waves induced to the analyzed samples. Rapid, non-destructive characterization of 3D micro-structures are limited in terms of geometrical features and optical properties of the sample. We suggest a method which is based on temporal tracking of secondary speckle patterns generated when illuminating a sample with a laser probe while applying known periodic vibration using an ultrasound transmitter. In this paper we investigated lasers drilled through glass vias. The large aspect ratios of the vias possess a challenge for traditional microscopy techniques in analyzing depth and taper profiles of the vias. The correlation of the amplitude vibrations to the vias depths is experimentally demonstrated.

We experimentally verify a speckle-based technique for noncontact measurement of glucose concentration in the bloodstream. The final device is intended to be a single wristwatch-style device containing a laser, a camera, and an alternating current (ac) electromagnet generated by a solenoid. The experiments presented are performed in vitro as proof of the concept. When a glucose substance is inserted into a solenoid generating an ac magnetic field, it exhibits Faraday rotation, which affects the temporal changes of the secondary speckle pattern distributions. 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.