Measuring human cerebral blood flow and brain function with fiber-based speckle contrast optical spectroscopy system.

Cerebral blood flow (CBF) is crucial for brain health. Speckle contrast optical spectroscopy (SCOS) is a technique that has been recently developed to measure CBF, but the use of SCOS to measure human brain function at large source-detector separations with comparable or greater sensitivity to cerebral rather than extracerebral blood flow has not been demonstrated. We describe a fiber-based SCOS system capable of measuring human brain activation induced CBF changes at 33 mm source detector separations using CMOS detectors. The system implements a pulsing strategy to improve the photon flux and uses a data processing pipeline to improve measurement accuracy. We show that SCOS outperforms the current leading optical modality for measuring CBF, i.e. diffuse correlation spectroscopy (DCS), achieving more than 10x SNR improvement at a similar financial cost. Fiber-based SCOS provides an alternative approach to functional neuroimaging for cognitive neuroscience and health science applications.

Field programmable gate array compression for large array multispeckle diffuse correlation spectroscopy.

Significance: Diffuse correlation spectroscopy (DCS) is an indispensable tool for quantifying cerebral blood flow noninvasively by measuring the autocorrelation function (ACF) of the diffused light. Recently, a multispeckle DCS approach was proposed to scale up the sensitivity with the number of independent speckle measurements, leveraging the rapid development of single-photon avalanche diode (SPAD) cameras. However, the extremely high data rate from advanced SPAD cameras is beyond the data transfer rate commonly available and requires specialized high-performance computation to calculate large number of autocorrelators (ACs) for real-time measurements. Aim: We aim to demonstrate a data compression scheme in the readout field-programmable gate array (FPGA) of a large-pixel-count SPAD camera. On-FPGA, data compression should democratize SPAD cameras and streamline system integration for multispeckle DCS. Approach: We present a 192×128 SPAD array with 128 linear ACs embedded on an FPGA to calculate 12,288 ACFs in real time. Results: We achieved a signal-to-noise ratio (SNR) gain of 110 over a single-pixel DCS system and more than threefold increase in SNR with respect to the state-of-the-art multispeckle DCS. Conclusions: The FPGA-embedded autocorrelation algorithm offers a scalable data compression method to large SPAD array, which can improve the sensitivity and usability of multispeckle DCS instruments.

Simultaneous photoplethysmography and blood flow measurements towards the estimation of blood pressure using speckle contrast optical spectroscopy.

Non-invasive continuous blood pressure monitoring remains elusive. There has been extensive research using the photoplethysmographic (PPG) waveform for blood pressure estimation, but improvements in accuracy are still needed before clinical use. Here we explored the use of an emerging technique, speckle contrast optical spectroscopy (SCOS), for blood pressure estimation. SCOS provides measurements of both blood volume changes (PPG) and blood flow index (BFi) changes during the cardiac cycle, and thus provides a richer set of parameters compared to traditional PPG. SCOS measurements were taken on the finger and wrists of 13 subjects. We investigated the correlations between features extracted from both the PPG and BFi waveforms with blood pressure. Features from the BFi waveforms were more significantly correlated with blood pressure than PPG features ( R = - 0.55, p = 1.1 × 10-4 for the top BFi feature versus R = - 0.53, p = 8.4 × 10-4 for the top PPG feature). Importantly, we also found that features combining BFi and PPG data were highly correlated with changes in blood pressure ( R = - 0.59, p = 1.7 × 10-4 ). These results suggest that the incorporation of BFi measurements should be further explored as a means to improve blood pressure estimation using non-invasive optical techniques.

Massively parallel, real-time multispeckle diffuse correlation spectroscopy using a 500 × 500 SPAD camera.

Diffuse correlation spectroscopy (DCS) is a promising noninvasive technique for monitoring cerebral blood flow and measuring cortex functional activation tasks. Taking multiple parallel measurements has been shown to increase sensitivity, but is not easily scalable with discrete optical detectors. Here we show that with a large 500 × 500 SPAD array and an advanced FPGA design, we achieve an SNR gain of almost 500 over single-pixel mDCS performance. The system can also be reconfigured to sacrifice SNR to decrease correlation bin width, with 400 ns resolution being demonstrated over 8000 pixels.

Development of a Monte Carlo-wave model to simulate time domain diffuse correlation spectroscopy measurements from first principles.

SIGNIFICANCE: Diffuse correlation spectroscopy (DCS) is an optical technique that measures blood flow non-invasively and continuously. The time-domain (TD) variant of DCS, namely, TD-DCS has demonstrated a potential to improve brain depth sensitivity and to distinguish superficial from deeper blood flow by utilizing pulsed laser sources and a gating strategy to select photons with different pathlengths within the scattering tissue using a single source-detector separation. A quantitative tool to predict the performance of TD-DCS that can be compared with traditional continuous wave DCS (CW-DCS) currently does not exist but is crucial to provide guidance for the continued development and application of these DCS systems. AIMS: We aim to establish a model to simulate TD-DCS measurements from first principles, which enables analysis of the impact of measurement noise that can be utilized to quantify the performance for any particular TD-DCS system and measurement geometry. APPROACH: We have integrated the Monte Carlo simulation describing photon scattering in biological tissue with the wave model that calculates the speckle intensity fluctuations due to tissue dynamics to simulate TD-DCS measurements from first principles. RESULTS: Our model is capable of simulating photon counts received at the detector as a function of time for both CW-DCS and TD-DCS measurements. The effects of the laser coherence, instrument response function, detector gate delay, gate width, intrinsic noise arising from speckle statistics, and shot noise are incorporated in the model. We have demonstrated the ability of our model to simulate TD-DCS measurements under different conditions, and the use of our model to compare the performance of TD-DCS and CW-DCS under a few typical measurement conditions. CONCLUSION: We have established a Monte Carlo-Wave model that is capable of simulating CW-DCS and TD-DCS measurements from first principles. In our exploration of the parameter space, we could not find realistic measurement conditions under which TD-DCS outperformed CW-DCS. However, the parameter space for the optimization of the contrast to noise ratio of TD-DCS is large and complex, so our results do not imply that TD-DCS cannot indeed outperform CW-DCS under different conditions. We made our code available publicly for others in the field to find use cases favorable to TD-DCS. TD-DCS also provides a promising way to measure deep brain tissue dynamics using a short source-detector separation, which will benefit the development of technologies including high density DCS systems and image reconstruction using a limited number of source-detector pairs.

Model of dynamic speckle evolution for evaluating laser speckle contrast measurements of tissue dynamics.

We introduce a dynamic speckle model (DSM) to simulate the temporal evolution of fully developed speckle patterns arising from the interference of scattered light reemitted from dynamic tissue. Using this numerical tool, the performance of laser speckle contrast imaging (LSCI) or speckle contrast optical spectroscopy (SCOS) systems which quantify tissue dynamics using the spatial contrast of the speckle patterns with a certain camera exposure time is evaluated. We have investigated noise sources arising from the fundamental speckle statistics due to the finite sampling of the speckle patterns as well as those induced by experimental measurement conditions including shot noise, camera dark and read noise, and calibrated the parameters of an analytical noise model initially developed in the fundamental or shot noise regime that quantifies the performance of SCOS systems using the number of independent observables (NIO). Our analysis is particularly focused on the low photon flux regime relevant for human brain measurements, where the impact of shot noise and camera read noise can become significant. Our numerical model is also validated experimentally using a novel fiber based SCOS (fb-SCOS) system for a dynamic sample. We have found that the signal-to-noise ratio (SNR) of fb-SCOS measurements plateaus at a camera exposure time, which marks the regime where shot and fundamental noise dominates over camera read noise. For a fixed total measurement time, there exists an optimized camera exposure time if temporal averaging is utilized to improve SNR. For a certain camera exposure time, photon flux value, and camera noise properties, there exists an optimized speckle-to-pixel size ratio (s/p) at which SNR is maximized. Our work provides the design principles for any LSCI or SCOS systems given the detected photon flux and properties of the instruments, which will guide the experimental development of a high-quality, low-cost fb-SCOS system that monitors human brain blood flow and functions.

Measuring neuronal activity with diffuse correlation spectroscopy: a theoretical investigation.

Significance: Diffuse correlation spectroscopy (DCS) measures cerebral blood flow non-invasively. Variations in blood flow can be used to detect neuronal activities, but its peak has a latency of a few seconds, which is slow for real-time monitoring. Neuronal cells also deform during activation, which, in principle, can be utilized to detect neuronal activity on fast timescales (within 100 ms) using DCS. Aims: We aim to characterize DCS signal variation quantified as the change of the decay time of the speckle intensity autocorrelation function during neuronal activation on both fast (within 100 ms) and slow (100 ms to seconds) timescales. Approach: We extensively modeled the variations in the DCS signal that are expected to arise from neuronal activation using Monte Carlo simulations, including the impacts of neuronal cell motion, vessel wall dilation, and blood flow changes. Results: We found that neuronal cell motion induces a DCS signal variation of ∼ 10 - 5 . We also estimated the contrast and number of channels required to detect hemodynamic signals at different time delays. Conclusions: From this extensive analysis, we do not expect to detect neuronal cell motion using DCS in the near future based on current technology trends. However, multi-channel DCS will be able to detect hemodynamic response with sub-second latency, which is interesting for brain-computer interfaces.

Choosing an optimal wavelength to detect brain activity in functional near-infrared spectroscopy.

Functional near-infrared spectroscopy (fNIRS) measures human brain function noninvasively. The optical response to oxy- and deoxy-hemoglobin concentration variations during brain activation is wavelength dependent because of the differing spectral shapes of the extinction coefficients of the two hemoglobin species. Choosing the optimal wavelength in fNIRS measurements is crucial to improving the performance of the technique. Here we report on a framework to estimate the spectral response to neural activation in a pre-defined local region. We found that the wavelength that exhibits the largest fractional change in the detected fluence with respect to the baseline value is around 830 nm.

High-sensitivity multispeckle diffuse correlation spectroscopy.

Significance: Cerebral blood flow is an important biomarker of brain health and function as it regulates the delivery of oxygen and substrates to tissue and the removal of metabolic waste products. Moreover, blood flow changes in specific areas of the brain are correlated with neuronal activity in those areas. Diffuse correlation spectroscopy (DCS) is a promising noninvasive optical technique for monitoring cerebral blood flow and for measuring cortex functional activation tasks. However, the current state-of-the-art DCS adoption is hindered by a trade-off between sensitivity to the cortex and signal-to-noise ratio (SNR). Aim: We aim to develop a scalable method that increases the sensitivity of DCS instruments. Approach: We report on a multispeckle DCS (mDCS) approach that is based on a 1024-pixel single-photon avalanche diode (SPAD) camera. Our approach is scalable to > 100,000 independent speckle measurements since large-pixel-count SPAD cameras are becoming available, owing to the investments in LiDAR technology for automotive and augmented reality applications. Results: We demonstrated a 32-fold increase in SNR with respect to traditional single-speckle DCS. Conclusion: A mDCS system that is based on a SPAD camera serves as a scalable method toward high-sensitivity DCS measurements, thus enabling both high sensitivity to the cortex and high SNR.

Optically Addressing Single Rare-Earth Ions in a Nanophotonic Cavity.

We demonstrate optical probing of spectrally resolved single Nd^{3+} rare-earth ions in yttrium orthovanadate. The ions are coupled to a photonic crystal resonator and show strong enhancement of the optical emission rate via the Purcell effect, resulting in near radiatively limited single photon emission. The measured high coupling cooperativity between a single photon and the ion allows for the observation of coherent optical Rabi oscillations. This could enable optically controlled spin qubits, quantum logic gates, and spin-photon interfaces for future quantum networks.

Ultra-sensitive mid-infrared emission spectrometer with sub-ns temporal resolution.

We evaluate the performance of a mid-infrared emission spectrometer operating at wavelengths between 1.5 and 6 µm based on an amorphous tungsten silicide (a-WSi) superconducting nanowire single-photon detector (SNSPD). We performed laser induced fluorescence spectroscopy of surface adsorbates with sub-monolayer sensitivity and sub-nanosecond temporal resolution. We discuss possible future improvements of the SNSPD-based infrared emission spectrometer and its potential applications in molecular science.

Nanophotonic rare-earth quantum memory with optically controlled retrieval.

Optical quantum memories are essential elements in quantum networks for long-distance distribution of quantum entanglement. Scalable development of quantum network nodes requires on-chip qubit storage functionality with control of the readout time. We demonstrate a high-fidelity nanophotonic quantum memory based on a mesoscopic neodymium ensemble coupled to a photonic crystal cavity. The nanocavity enables >95% spin polarization for efficient initialization of the atomic frequency comb memory and time bin-selective readout through an enhanced optical Stark shift of the comb frequencies. Our solid-state memory is integrable with other chip-scale photon source and detector devices for multiplexed quantum and classical information processing at the network nodes.

Mid-infrared Laser-Induced Fluorescence with Nanosecond Time Resolution Using a Superconducting Nanowire Single-Photon Detector: New Technology for Molecular Science.

In contrast to UV photomultiplier tubes that are widely used in physical chemistry, mid-infrared detectors are notorious for poor sensitivity and slow time response. This helps explain why, despite the importance of infrared spectroscopy in molecular science, mid-infrared fluorescence is not more widely used. In recent years, several new technologies have been developed that open new experimental possibilities for research in the mid-infrared. In this Account, we present one of the more promising technologies, superconducting nanowire single photon detectors (SNSPDs) by sharing our experience with its use in a typical experiment carried out by physical chemists (laser-induced fluorescence) and comparing the SNSPD to a detector commonly used by physical chemists (InSb at LN Temperature). SNSPDs are fabricated from a thin film of superconducting metal, patterned into a meandering nanowire. The nanowire is cooled below its superconducting temperature, Tc, and held in a constant current circuit below the critical current necessary to destroy superconductivity, Ic. Upon absorption of a photon, the resulting heat is sufficient to destroy superconductivity across the entire width of the nanowire, an event that can be detected as a voltage pulse. In contrast to semiconductor-based detectors, which have a long wavelength cutoff determined by the band gap, the SNSPD exhibits single-photon sensitivity across the entire mid-IR spectrum. As these devices have not been used extensively outside the field of light detection technology research, one important goal of this Account is to provide practical details for the implementation of these devices in a physical chemistry laboratory. We provide extensive Supporting Information describing what is needed. This includes information on a liquid nitrogen cooled monochromator, the optical collection system including mid-infrared fibers, as well as a closed-cycle cryogenic cooler that reaches 0.3 K. We demonstrate the advantages of these detectors in a time-resolved laser-induced infrared fluorescence experiment on the energy pooling in crystalline CO overlayers formed on a NaCl(100) surface. We present dispersed fluorescence spectra recorded from 1.9 to 7.0 µm obtained by single-photon counting. We also estimate the sensitivity of this WSi-based detection system at 3 µm; the system's noise equivalent power (NEP) value is ∼10-3 of a conventional InSb photovoltaic device. Straightforward modifications are expected to provide another 100 000-fold improvement. We demonstrate that the temporal resolution of the experiment is limited only by the pulse duration of the laser used in this work (fwhm = 3.7 ns). The use of SNSPDs enables dramatically improved observations of energy pooling in cryogenic molecular crystals.

Temporal Multimode Storage of Entangled Photon Pairs.

Multiplexed quantum memories capable of storing and processing entangled photons are essential for the development of quantum networks. In this context, we demonstrate and certify the simultaneous storage and retrieval of two entangled photons inside a solid-state quantum memory and measure a temporal multimode capacity of ten modes. This is achieved by producing two polarization-entangled pairs from parametric down-conversion and mapping one photon of each pair onto a rare-earth-ion-doped (REID) crystal using the atomic frequency comb (AFC) protocol. We develop a concept of indirect entanglement witnesses, which can be used as Schmidt number witnesses, and we use it to experimentally certify the presence of more than one entangled pair retrieved from the quantum memory. Our work puts forward REID-AFC as a platform compatible with temporal multiplexing of several entangled photon pairs along with a new entanglement certification method, useful for the characterization of multiplexed quantum memories.

High-efficiency WSi superconducting nanowire single-photon detectors for quantum state engineering in the near infrared.

We report on high-efficiency superconducting nanowire single-photon detectors based on amorphous tungsten silicide and optimized at 1064 nm. At an operating temperature of 1.8 K, we demonstrated a 93% system detection efficiency at this wavelength with a dark noise of a few counts per second. Combined with cavity-enhanced spontaneous parametric downconversion, this fiber-coupled detector enabled us to generate narrowband single photons with a heralding efficiency greater than 90% and a high spectral brightness of 0.6×104 photons/(s·mW·MHz). Beyond single-photon generation at large rate, such high-efficiency detectors open the path to efficient multiple-photon heralding and complex quantum state engineering.

A multiplexed light-matter interface for fibre-based quantum networks.

Processing and distributing quantum information using photons through fibre-optic or free-space links are essential for building future quantum networks. The scalability needed for such networks can be achieved by employing photonic quantum states that are multiplexed into time and/or frequency, and light-matter interfaces that are able to store and process such states with large time-bandwidth product and multimode capacities. Despite important progress in developing such devices, the demonstration of these capabilities using non-classical light remains challenging. Here, employing the atomic frequency comb quantum memory protocol in a cryogenically cooled erbium-doped optical fibre, we report the quantum storage of heralded single photons at a telecom-wavelength (1.53 µm) with a time-bandwidth product approaching 800. Furthermore, we demonstrate frequency-multimode storage and memory-based spectral-temporal photon manipulation. Notably, our demonstrations rely on fully integrated quantum technologies operating at telecommunication wavelengths. With improved storage efficiency, our light-matter interface may become a useful tool in future quantum networks.

Heralded amplification of photonic qubits.

We demonstrate postselection free heralded qubit amplification for Time-Bin qubits and single photon states in an all-fibre, telecom-wavelength, scheme that highlights the simplicity, stability and potential for fully integrated photonic solutions. Exploiting high-efficiency superconducting detectors, the gain, fidelity and the performance of the amplifier are studied as a function of loss. We also demonstrate the first heralded single photon amplifier with independent sources. This provides a significant advance towards demonstrating device-independent quantum key distribution as well as fundamental tests of quantum mechanics over extended distances.

Telecom-Wavelength Atomic Quantum Memory in Optical Fiber for Heralded Polarization Qubits.

Polarization-encoded photons at telecommunication wavelengths provide a compelling platform for practical realizations of photonic quantum information technologies due to the ease of performing single qubit manipulations, the availability of polarization-entangled photon-pair sources, and the possibility of leveraging existing fiber-optic links for distributing qubits over long distances. An optical quantum memory compatible with this platform could serve as a building block for these technologies. Here we present the first experimental demonstration of an atomic quantum memory that directly allows for reversible mapping of quantum states encoded in the polarization degree of freedom of a telecom-wavelength photon. We show that heralded polarization qubits at a telecom wavelength are stored and retrieved with near-unity fidelity by implementing the atomic frequency comb protocol in an ensemble of erbium atoms doped into an optical fiber. Despite remaining limitations in our proof-of-principle demonstration such as small storage efficiency and storage time, our broadband light-matter interface reveals the potential for use in future quantum information processing.

Phonon counting and intensity interferometry of a nanomechanical resonator.

In optics, the ability to measure individual quanta of light (photons) enables a great many applications, ranging from dynamic imaging within living organisms to secure quantum communication. Pioneering photon counting experiments, such as the intensity interferometry performed by Hanbury Brown and Twiss to measure the angular width of visible stars, have played a critical role in our understanding of the full quantum nature of light. As with matter at the atomic scale, the laws of quantum mechanics also govern the properties of macroscopic mechanical objects, providing fundamental quantum limits to the sensitivity of mechanical sensors and transducers. Current research in cavity optomechanics seeks to use light to explore the quantum properties of mechanical systems ranging in size from kilogram-mass mirrors to nanoscale membranes, as well as to develop technologies for precision sensing and quantum information processing. Here we use an optical probe and single-photon detection to study the acoustic emission and absorption processes in a silicon nanomechanical resonator, and perform a measurement similar to that used by Hanbury Brown and Twiss to measure correlations in the emitted phonons as the resonator undergoes a parametric instability formally equivalent to that of a laser. Owing to the cavity-enhanced coupling of light with mechanical motion, this effective phonon counting technique has a noise equivalent phonon sensitivity of 0.89 ± 0.05. With straightforward improvements to this method, a variety of quantum state engineering tasks using mesoscopic mechanical resonators would be enabled, including the generation and heralding of single-phonon Fock states and the quantum entanglement of remote mechanical elements.

On-chip detection of non-classical light by scalable integration of single-photon detectors.

Photonic-integrated circuits have emerged as a scalable platform for complex quantum systems. A central goal is to integrate single-photon detectors to reduce optical losses, latency and wiring complexity associated with off-chip detectors. Superconducting nanowire single-photon detectors (SNSPDs) are particularly attractive because of high detection efficiency, sub-50-ps jitter and nanosecond-scale reset time. However, while single detectors have been incorporated into individual waveguides, the system detection efficiency of multiple SNSPDs in one photonic circuit-required for scalable quantum photonic circuits-has been limited to <0.2%. Here we introduce a micrometer-scale flip-chip process that enables scalable integration of SNSPDs on a range of photonic circuits. Ten low-jitter detectors are integrated on one circuit with 100% device yield. With an average system detection efficiency beyond 10%, and estimated on-chip detection efficiency of 14-52% for four detectors operated simultaneously, we demonstrate, to the best of our knowledge, the first on-chip photon correlation measurements of non-classical light.