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

Abstract

. 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, 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 quasi-Gaussian pulse obtained using electro-optic laser shaping providing the best results.

Superconducting nanowire single-photon sensing of cerebral blood flow

“…The MCX software package 23 was used to simulate photon transport and momentum transfer in a realistic brain geometry. 24 For this forward model, we used a four-layer MRI-derived volumetric geometry segmented into scalp, skull, cerebrospinal fluid (CSF), gray, and white matter (brain), with spatial resolution. For each of the four tissue types, we used the optical properties and reported in Table 2 .…”

Functional Time Domain Diffuse Correlation Spectroscopy

“…As in TD-NIRS, in TD-DCS photons are selected by their time-of-flight (ToF). This method allows for the rejection of short pathlength photons that travel mostly in extracerebral layers (i.e., scalp and skull), while keeping the longer pathlength photons that travel deeper and reach the brain ( Cheng et al, 2018 ; Mazumder et al, 2021 ). A major benefit of this ToF selectivity is that shorter SD separations can be used, improving upon the SNR and spatial resolution of the measurements.…”

“…This further requires the use of photodetectors with low jitter and a sharp temporal response over multiple decades (i.e., lacking a “diffusion tail”). The importance and impact of these instrumentation related factors have been explored by our group and others through both simulations ( Qiu et al, 2018 , 2021 ; Colombo et al, 2019 ; Mazumder et al, 2021 ) and experiments ( Tamborini et al, 2019 ; Samaei et al, 2021a ).…”

“…Previously reported TD-DCS systems ( Pagliazzi et al, 2017 ; Tamborini et al, 2019 ; Colombo et al, 2020 ; Samaei et al, 2021b ) face limitations with respect to detector efficiency and/or the characteristics of the IRF. To address these limitations, and building on our previous work demonstrating the benefits of DCS measurements at 1,064 nm ( Carp et al, 2020 ; Ozana et al, 2021 ), as well as simulation studies by our group ( Mazumder et al, 2021 ) and others ( Qiu et al, 2018 , 2021 ; Colombo et al, 2019 ) indicating the importance of optimizing laser source characteristics for TD-DCS, we developed a high-performance, next-generation TD-DCS system employing a custom 1,064 nm laser source and superconducting nanowire single photon detectors (SNSPDs, overall size of 69 × 49.5 × 113 cm for depth, width, and height, respectively) to maximize measurement performance and enable functional brain imaging. The laser source can deliver an optimized, quasi-transform limited ∼300 ps full width half max (FWHM) laser pulse with average power in excess of 500 mW at 1,064 nm.…”

First-in-clinical application of a time-gated diffuse correlation spectroscopy system at 1064nm using superconducting nanowire single photon detectors

“…This reduces the size of the probe for (3) greater compactness. Short-wave infrared (SWIR) wavelengths such as1064 nm has a low effective attenuation in brain tissue [44], [47], [53], [54], which (4) increases the tissue probing depth, and allows for a higher maximum permissible laser power (ANSI Z136.1 [61]) to (5) increase the SNR. Very recently we demonstrated the clinical feasibility of using a new generation photon counting detector, superconducting nanowire single photon detector (SNSPD) for CW-DCS with improved SNR at use of a SWIR wavelength at 1064 nm in a patient with severe TBI in an ICU setting.…”