Functional near-infrared spectroscopy (fNIRS) and diffuse correlation spectroscopy (DCS) have shown promise as non-invasive optical methods for cerebral functional imaging. DCS approaches currently have limited sensitivity in adults. fNIRS sensitivity is also limited, particularly in high-detector-density applications. Sensitivity can be improved using temporal discrimination (TD), where the laser excitation is of short (~400ps) duration and the detector rejects early photons that have not penetrated into the brain while maintain high sensitivity to those that have. We report here on the development of a novel 32x32 Single-Photon Avalanche photo-Detector (SPAD) array and Read-Out Integrated Circuit (ROIC) that can operate in either the visible or NIR enabling high-channel-count TD-fNIRS or TD-DCS systems.
Diffuse correlation spectroscopy (DCS) is an emerging near infrared spectroscopy modality able to measure cerebral blood flow (CBF) non-invasively and continuously in humans. We have reported a limited applicability in adults due to the significant extracerebral tissue thickness and the low signal-to-noise ratio (SNR) of the measurements. Improvements to DCS brain sensitivity and SNR can be achieved by operating DCS at 1064 and using superconducting nanowire single-photon detectors (SNSPDs). Initial human results show a 16-fold improvement in SNR and 20% improvement in depth sensitivity. This allows us to resolve changes in CBF in adult subjects more robustly and accurately than was previously achievable.
We present the design of an innovative time-gated 32×32 InP/InGaAs-based Single Photon Avalanche Diode (SPAD) array with sub-nanosecond gating capabilities operating up to 10MHz repetition rate specifically designed for time-domain diffuse correlation spectroscopy at 1064nm. We present the detector design, experimental characterization and preliminary validations on a liquid phantom. This testing is informing us for a revision of the photodetector which will allow to reach up to 192 optical channels towards functional blood flow changes measurements with full head coverage with improved brain sensitivity thanks to early-photons rejection.
We present the design of an innovative instrument for time-gated diffuse correlation spectroscopy. It features a 1064nm pulsed sub-ns long coherence-length laser operating up to 75MHz, a 100-channel in-FPGA correlator and a novel time-gated 32×32 InP/InGaAs-based Single Photon Avalanche Diode (SPAD) array with sub-nanosecond gating capabilities operating up to 10MHz repetition rate. We present components experimental characterization and preliminary validations on a liquid phantom. This testing is informing us for a revision of the photodetector which will allow to reach up to 192 optical channels towards functional blood flow changes measurements with full head coverage.
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.
KEYWORDS: Blood circulation, Absorption, Scattering, Signal to noise ratio, Tissue optics, Near infrared spectroscopy, Spectroscopy, Tissues, Signal attenuation, Sensors
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.
KEYWORDS: Photons, Blood, Liver, Tissue optics, Signal to noise ratio, Tissues, Monte Carlo methods, Near infrared spectroscopy, Computer simulations, Picosecond phenomena
Time-domain near-infrared spectroscopy (TD-NIRs) and Time-Domain Diffuse Correlation Spectroscopy (TD-DCS) are emerging imaging techniques that use a near-infrared, long coherence, pulsed laser to characterize oxygenation levels and blood flow. TD-DCS is a promising tool for bedside monitoring of brain activity due to its high time-resolution and portability. One potential new application area for TD-DCS is for detecting non-compressible torso hemorrhages (NCTH). NCTH is a serious traumatic injury that requires surgical intervention and is a leading cause of death in the military due to the lack of a rapid and portable imaging system sensitive enough to detect injury. Applying long wavelengths (1064 nm and 1120 nm) and time gating, TD-DCS can penetrate the superficial tissue layers and potentially detect bleeding deep within an organ. One limitation of current time-gating system is its reliance on full knowledge of the target tissue layers and properties in order to apply gating effectively. An automatic gating scheme that can adjust the time gate to quickly recalibrate itself to different imaging conditions, such as a different body area, can eliminate this limitation. Here, we use modeling and Monte Carlo simulations to search for characteristics in return signal profiles, specifically the time-of-flight and intensity profiles, as first step toward an automatic time-gating algorithm. We detail the simulation setups, parameter sweeps, and preliminary results in this report. These results show promise for TD-DCS as a tool for rapid and continuous monitoring of injuries in the field.
Our team has recently shown the SNR and depth-sensitivity advantages of using 1064 nm light for diffuse correlation spectroscopy as well as the challenges of commercially available single-photon detectors at this wavelength. We will review two strategies for custom readout integrated circuit designs that simultaneously target lower pixel dead times and lower afterpulsing probabilities. Both designs use macropixels comprising many detectors, each having a programmable hold-off time. We will compare simulated autocorrelations for our detector models and compare predicted performance against commercial InGaAs/InP detectors.
Smart pixel imaging with computational-imaging arrays (SPICA) transfers image plane coding typically realized in the optical architecture to the digital domain of the focal plane array, thereby minimizing signal-to-noise losses associated with static filters or apertures and inherent diffraction concerns. MIT Lincoln Laboratory has been developing digitalpixel focal plane array (DFPA) devices for many years. In this work, we leverage legacy designs modified with new features to realize a computational imaging array (CIA) with advanced pixel-processing capabilities. We briefly review the use of DFPAs for on-chip background removal and image plane filtering. We focus on two digital readout integrated circuits (DROICS) as CIAs for two-dimensional (2D) transient target tracking and three-dimensional (3D) transient target estimation using per-pixel coded-apertures or flutter shutters. This paper describes two DROICs – a SWIR pixelprocessing imager (SWIR-PPI) and a Visible CIA (VISCIA). SWIR-PPI is a DROIC with a 1 kHz global frame rate with a maximum per-pixel shuttering rate of 100 MHz, such that each pixel can be modulated by a time-varying, pseudorandom, and duo-binary signal (+1,-1,0). Combining per-pixel time-domain coding and processing enables 3D (x,y,t) target estimation with limited loss of spatial resolution. We evaluate structured and pseudo-random encoding strategies and employ linear inversion and non-linear inversion using total-variation minimization to estimate a 3D data cube from a single 2D temporally-encoded measurement. The VISCIA DROIC, while low-resolution, has a 6 kHz global frame rate and simultaneously encodes eight periodic or aperiodic transient target signatures at a maximum rate of 50 MHz using eight 8-bit counters. By transferring pixel-based image plane coding to the DROIC and utilizing sophisticated processing, our CIAs enable on-chip temporal super-resolution.
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