Functional Time Domain Diffuse Correlation Spectroscopy

Abstract

Time-domain diffuse correlation spectroscopy (TD-DCS) offers a novel approach to high-spatial resolution functional brain imaging based on the direct quantification of cerebral blood flow (CBF) changes in response to neural activity. However, the signal-to-noise ratio (SNR) offered by previous TD-DCS instruments remains a challenge to achieving the high temporal resolution needed to resolve perfusion changes during functional measurements. Here we present a next-generation optimized functional TD-DCS system that combines a custom 1,064 nm pulse-shaped, quasi transform-limited, amplified laser source with a high-resolution time-tagging system and superconducting nanowire single-photon detectors (SNSPDs). System characterization and optimization was conducted on homogenous and two-layer intralipid phantoms before performing functional CBF measurements in six human subjects. By acquiring CBF signals at over 5 Hz for a late gate start time of the temporal point spread function (TPSF) at 15 mm source-detector separation, we demonstrate for the first time the measurement of blood flow responses to breath-holding and functional tasks using TD-DCS.

Interferometric near-infrared spectroscopy (iNIRS) reveals that blood flow index depends on wavelength

“…Here the absolute medium “EARLY”, “MID” and “LATE” τ s are 60, 330 and 500 ps, respectively. This definition of time gates is consistent with previous DCS literature [ 28 , 44 ].…”

“…BFI is a proxy for nutritive blood flow, and correlates with conventional perfusion metrics [ 4 – 13 ]. BFI is typically measured in the wavelength range from 767-855 nm [ 14 – 24 ], though there is a growing push in the DCS field to measure around 1064 nm, a wavelength range which confers several benefits [ 25 – 28 ]. To the extent that BFI is a valid proxy for tissue perfusion, one expects that it should not depend on the wavelength of light used to probe tissue.…”

Diffuse correlation spectroscopy: current status and future outlook

“…However, the lack of suitable semiconductor photon counting detectors represents a significant challenge, and initial demonstrations have used superconducting nanowire devices that are cryocooled and hence expensive and noisy. 60 , 61 …”

“…However, the lack of suitable semiconductor photon counting detectors represents a significant challenge, and initial demonstrations have used superconducting nanowire devices that are cryocooled and hence expensive and noisy. 60,61 3.1.6 Summary DCS and related techniques are the focus of intense technical development activities as described above and summarized in Table 1. Many of these approaches can potentially be combined to compound benefits, and several orders of magnitude improvements in SNR are likely; this can translate to faster acquisition rates and/or the ability to conduct measurements at larger sourcedetector separations with higher brain sensitivity.…”

Investigating the impact of fast count rates on timing jitter in SNSPDs

“…Superconducting nanowire single-photon detectors (SNSPDs) have proven themselves as a valuable tool for photonics through their very high detection efficiency, 1 very low dark count rates, 2 high counting rates, 3 excellent timing precision, 4,5 and newly widespread commercial availability. The combination of all these state-of-the-art performance parameters into a single sensor technology has enabled advances in a diverse collection of fields such as free-space optical communications, 6,7 biomedical optics, [8][9][10] spectroscopy, 11 and quantum information. [12][13][14] However, it is important to note that these capabilities are all accessible by a single sensor within certain limits.…”