Abstract

Infrared light scattering methods have been developed and employed to non-invasively monitor human cerebral blood flow (CBF). However, the number of reflected photons that interact with the brain is low when detecting blood flow in deep tissue. To tackle this photon-starved problem, we present and demonstrate the idea of interferometric speckle visibility spectroscopy (ISVS). In ISVS, an interferometric detection scheme is used to boost the weak signal light. The blood flow dynamics are inferred from the speckle statistics of a single frame speckle pattern. We experimentally demonstrated the improvement in the measurement of fidelity by introducing interferometric detection when the signal photon number is low. We apply the ISVS system to monitor the human CBF in situations where the light intensity is ∼100-fold less than that in common diffuse correlation spectroscopy (DCS) implementations. Due to the large number of pixels (∼2 × 105) used to capture light in the ISVS system, we are able to collect a similar number of photons within one exposure time as in normal DCS implementations. Our system operates at a sampling rate of 100 Hz. At the exposure time of 2 ms, the average signal photoelectron number is ∼0.95 count/pixel, yielding a single pixel interferometric measurement signal-to-noise ratio (SNR) of ∼0.97. The total ∼2 × 105 pixels provide an expected overall SNR of 436. We successfully demonstrate that the ISVS system is able to monitor the human brain pulsatile blood flow, as well as the blood flow change when a human subject is doing a breath-holding task.

Highlights

  • Over the last few decades, a variety of non-invasive optical schemes have been developed to study the cerebral blood flow (CBF) dynamics in human brains,1–4 including near-infrared spectroscopy (NIRS),1 diffuse correlation spectroscopy (DCS),2,3 and diffuse optical tomography (DOT).4 The 650 nm–950 nm optical window has relatively low optical absorption and, enables light to penetrate through the skin, scalp, and skull and interact with the brain

  • The interferometric speckle visibility spectroscopy (ISVS) principle is based on an interferometer, where the weak diffused light containing the information is boosted by using a reference beam and recorded by using the camera [see Fig. 1(a)]

  • Due to off-axis holography, the Fourier transform of It(r) in Eq (1) provides three separate lobes [see Fig. 1(A) of the supplementary material], where the central lobe is the Fourier transform of the DC terms [first two terms in Eq (1)] and the two side lobes are the Fourier transform of the interference term [the third term in Eq (1)]

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Summary

INTRODUCTION

Over the last few decades, a variety of non-invasive optical schemes have been developed to study the cerebral blood flow (CBF) dynamics in human brains, including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), and diffuse optical tomography (DOT). The 650 nm–950 nm optical window has relatively low optical absorption and, enables light to penetrate through the skin, scalp, and skull and interact with the brain. We propose and demonstrate the idea of interferometric SVS, or ISVS, which circumvents the camera noise problem and is able to measure the blood flow dynamics even when the number of available signal photons is limited (below 1 photoelectron per pixel). Interferometric detection is able to overcome camera noise by boosting the weak signal term in the heterodyne cross term, and as such, the ISVS system is able to achieve a reasonable SNR even when the mean pixel value number from the signal light is smaller than 1 This allows ISVS to perform measurements within a short acquisition time and a high rate at which CBF estimates are generated in a low-light condition where DCS fails to do so. We designed a breathholding task for a human subject and implemented ISVS to monitor the CBF, showing that the relative CBF (rCBF) changes in accordance to brain stimulation caused by the task could be revealed by ISVS

Principle
System characterization and measurement fidelity improvements
System operation on rats
Human experiment design and operation
DISCUSSION
Full Text
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