Open-source FlexNIRS: A low-cost, wireless and wearable cerebral health tracker.

Currently, there is great interest in making neuroimaging widely accessible and thus expanding the sampling population for better understanding and preventing diseases. The use of wearable health devices has skyrocketed in recent years, allowing continuous assessment of physiological parameters in patients and research cohorts. While most health wearables monitor the heart, lungs and skeletal muscles, devices targeting the brain are currently lacking. To promote brain health in the general population, we developed a novel, low-cost wireless cerebral oximeter called FlexNIRS. The device has 4 LEDs and 3 photodiode detectors arranged in a symmetric geometry, which allows for a self-calibrated multi-distance method to recover cerebral hemoglobin oxygenation (SO2) at a rate of 100 Hz. The device is powered by a rechargeable battery and uses Bluetooth Low Energy (BLE) for wireless communication. We developed an Android application for portable data collection and real-time analysis and display. Characterization tests in phantoms and human participants show very low noise (noise-equivalent power <70 fW/√Hz) and robustness of SO2 quantification in vivo. The estimated cost is on the order of $50/unit for 1000 units, and our goal is to share the device with the research community following an open-source model. The low cost, ease-of-use, smart-phone readiness, accurate SO2 quantification, real time data quality feedback, and long battery life make prolonged monitoring feasible in low resource settings, including typically medically underserved communities, and enable new community and telehealth applications.

Erratum: Improved accuracy of cerebral blood flow quantification in the presence of systemic physiology cross-talk using multi-layer Monte Carlo modeling.

[This corrects the article DOI: 10.1117/1.NPh.8.1.015001.].

Optimization of time domain diffuse correlation spectroscopy parameters for measuring brain blood flow.

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.

Improved accuracy of cerebral blood flow quantification in the presence of systemic physiology cross-talk using multi-layer Monte Carlo modeling.

Significance: Contamination of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow (CBF) due to systemic physiology remains a significant challenge in the clinical translation of DCS for neuromonitoring. Tunable, multi-layer Monte Carlo-based (MC) light transport models have the potential to remove extracerebral flow cross-talk in cerebral blood flow index ( CBF i ) estimates. Aim: We explore the effectiveness of MC DCS models in recovering accurate CBF i changes in the presence of strong systemic physiology variations during a hypercapnia maneuver. Approach: Multi-layer slab and head-like realistic (curved) geometries were used to run MC simulations of photon propagation through the head. The simulation data were post-processed into models with variable extracerebral thicknesses and used to fit DCS multi-distance intensity autocorrelation measurements to estimate CBF i timecourses. The results of the MC CBF i values from a set of human subject hypercapnia sessions were compared with CBF i values estimated using a semi-infinite analytical model, as commonly used in the field. Results: Group averages indicate a gradual systemic increase in blood flow following a different temporal profile versus the expected rapid CBF response. Optimized MC models, guided by several intrinsic criteria and a pressure modulation maneuver, were able to more effectively separate CBF i changes from scalp blood flow influence than the analytical fitting, which assumed a homogeneous medium. Three-layer models performed better than two-layer ones; slab and curved models achieved largely similar results, though curved geometries were closer to physiological layer thicknesses. Conclusion: Three-layer, adjustable MC models can be useful in separating distinct changes in scalp and brain blood flow. Pressure modulation, along with reasonable estimates of physiological parameters, can help direct the choice of appropriate layer thicknesses in MC models.

Diffuse correlation spectroscopy measurements of blood flow using 1064 nm light.

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.

Portable System for Time-Domain Diffuse Correlation Spectroscopy.

We introduce a portable system for clinical studies based on time-domain diffuse correlation spectroscopy (DCS). After evaluating different lasers and detectors, the final system is based on a pulsed laser with about 550 ps pulsewidth, a coherence length of 38 mm, and two types of single-photon avalanche diodes (SPAD). The higher efficiency of the red-enhanced SPAD maximizes detection of the collected light, increasing the signal-to-noise ratio, while the better timing response of the CMOS SPAD optimizes the selection of late photons and increases spatial resolution. We discuss component selection and performance, and we present a full characterization of the system, measurement stability, a phantom-based validation study, and preliminary in vivo results collected from the forearms and the foreheads of four healthy subjects. With this system, we are able to resolve blood flow changes 1 cm below the skin surface with improved depth sensitivity and spatial resolution with respect to continuous wave DCS.

Time domain diffuse correlation spectroscopy: modeling the effects of laser coherence length and instrument response function.

Diffuse correlation spectroscopy (DCS) is an optical technique that non-invasively quantifies an index of blood flow (BFi) by measuring the temporal autocorrelation function of the intensity fluctuations of light diffusely remitted from the tissue. Traditional DCS measurements use continuous wave (CW) lasers with coherence lengths longer than the photon path lengths in the sample to ensure that the diffusely remitted light is coherent and generates a speckle pattern. Recently, we proposed time domain DCS (TD-DCS) to allow measurements of the speckle fluctuations for specific path lengths of light through the tissue, which has the distinct advantage of permitting an analysis of selected long path lengths of light to improve the depth sensitivity of the measurement. However, compared to CW-DCS, factors including the instrument response function (IRF), the detection gate width, and the finite coherence length need to be considered in the model analysis of the experimental data. Here we present a TD-DCS model describing how the intensity autocorrelation functions measured for different path lengths of light depend on the coherence length, pulse width of the laser, detection gate width, IRF, BFi, and optical properties of the scattering sample. Predictions of the model are compared with experimental results using a homogeneous liquid phantom sample that mimics human tissue optical properties. The BFis obtained from the TD-DCS model for different path lengths of light agree with the BFi obtained from CW-DCS measurements, while the standard simplified model underestimates the BFi by a factor of ∼2. This Letter establishes the theoretical foundation of the TD-DCS technique and provides guidance for future BFi measurements in tissue.

Compact, multi-exposure speckle contrast optical spectroscopy (SCOS) device for measuring deep tissue blood flow.

Speckle contrast optical spectroscopy (SCOS) measures absolute blood flow in deep tissue, by taking advantage of multi-distance (previously reported in the literature) or multi-exposure (reported here) approach. This method promises to use inexpensive detectors to obtain good signal-to-noise ratio, but it has not yet been implemented in a suitable manner for a mass production. Here we present a new, compact, low power consumption, 32 by 2 single photon avalanche diode (SPAD) array that has no readout noise, low dead time and has high sensitivity in low light conditions, such as in vivo measurements. To demonstrate the capability to measure blood flow in deep tissue, healthy volunteers were measured, showing no significant differences from the diffuse correlation spectroscopy. In the future, this array can be miniaturized to a low-cost, robust, battery operated wireless device paving the way for measuring blood flow in a wide-range of applications from sport injury recovery and training to, on-field concussion detection to wearables.

Development and characterization of a multidistance and multiwavelength diffuse correlation spectroscopy system.

This paper presents a multidistance and multiwavelength diffuse correlation spectroscopy (DCS) approach and its implementation to simultaneously measure the optical proprieties of deep tissue as well as the blood flow. The system consists of three long coherence length lasers at different wavelengths in the near-infrared, eight single-photon detectors, and a correlator board. With this approach, we collect both light intensity and DCS data at multiple distances and multiple wavelengths, which provide unique information to fit for all the parameters of interest: scattering, blood flow, and hemoglobin concentration. We present the characterization of the system and its validation with phantom measurements.

Time-domain diffuse correlation spectroscopy.

Physiological monitoring of oxygen delivery to the brain has great significance for improving the management of patients at risk for brain injury. Diffuse correlation spectroscopy (DCS) is a rapidly growing optical technology able to non-invasively assess the blood flow index (BFi) at the bedside. The current limitations of DCS are the contamination introduced by extracerebral tissue and the need to know the tissue's optical properties to correctly quantify the BFi. To overcome these limitations, we have developed a new technology for time-resolved diffuse correlation spectroscopy. By operating DCS in the time domain (TD-DCS), we are able to simultaneously acquire the temporal point-spread function to quantify tissue optical properties and the autocorrelation function to quantify the BFi. More importantly, by applying time-gated strategies to the DCS autocorrelation functions, we are able to differentiate between short and long photon paths through the tissue and determine the BFi for different depths. Here, we present the novel device and we report the first experiments in tissue-like phantoms and in rodents. The TD-DCS method opens many possibilities for improved non-invasive monitoring of oxygen delivery in humans.