Pulsed ultrasound modulated optical tomography with increased optical/ultrasound pulse ratio

Abstract

A system and method of performing ultrasound modulated optical tomography. Ultrasound is delivered into a target voxel in an anatomical structure, and sample light is delivered into the anatomical structure, whereby a portion of the sample light passing through the target voxel is scattered by the biological tissue as signal light, and a portion of the sample light not passing through the target voxel is scattered by the anatomical structure as background light. The ultrasound and sample light are pulsed in synchrony, such that only the signal light is frequency shifted by the ultrasound. Multiple pulses of the sample light are delivered into the anatomical structure for each pulse of the ultrasound delivered into the target voxel. Reference light is combined with the signal light and background light to generate an interference light pattern, which is sequentially modulated to generate different interference light patterns, which are detected.

Description

RELATED APPLICATION DATA[0001]Pursuant to 35 U.S.C. § 119(e), this application claims the benefit of U.S. Provisional Patent Application 62 / 590,150, filed Nov. 22, 2017, and U.S. Provisional Patent Application 62 / 596,446, filed Dec. 8, 2017, which are expressly incorporated herein by reference. This application is also related to U.S. patent application Ser. No. 15 / ______ (Attorney Docket No. KNL-001US01) and U.S. patent application Ser. No. 15 / ______ (Attorney Docket No. KNL-001US03), filed on the same date, which are expressly incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to methods and systems for non-invasive measurements in the human body, and in particular, methods and systems related to detecting physiologically dependent optical parameters in the human body.BACKGROUND OF THE INVENTION[0003]Measuring neural activity in the brain is useful for medical diagnostics, neuromodulation therapies, neuroengineering, or brain-computer interf...

AI Technical Summary

Benefits of technology

[0015]PW UOT has the benefit of enabling improved axial resolution compared to CW UOT. That is, with CW UOT, any light passing through the tissue, even though outside of the focal voxel, may be inadvertently tagged by the continuously propagating ultrasound energy along the ultrasound axis, thereby decreasing the signal-to-noise

Problems solved by technology

Because DOT and fNIRS rely on light, which scatters many times inside brain, skull, dura, pia, and skin tissues, the light paths occurring in these techniques comprise random or “diffusive” walks, and therefore, only limited spatial resolution can be obtained by a conventional optical detector, often on the order of centimeters.

The reason for this limited spatial resolution is that the paths of photons striking the detector in such schemes are highly variable and difficult, and even impossible to predict without detailed microscopic knowledge of the scattering characteristics of the brain volume of interest, which is typically unavailable in practice (i.e., in the setting of non-invasive measurements through skull for brain imaging and brain interfacing).

Typical UOT implementations generate weak signals that make it difficult to differentiate ultrasound-tagged light passing through the focal voxel from a much larger amount of unmodulated light which is measured as DC shot noise.

Thus, conventional UOT has the challenge of obtaining optical information through several centimeters of biological tissue, for example, noninvasive measurements through the human skull used to measure functional changes in the brain.

In the context of neuroengineering and brain computer interfacing, a key challenge is to render these methods to be sufficiently sensitive to be useful for through-human-skull functional neuroimaging.

One technique uses a narrow spectral filter to separate out the untagged light striking a single-pixel detector, and is immune to speckle decorrelation (greater tha

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