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

The present invention relates to an ultrasound modulated optical tomography (UOT) system and method for non-invasive imaging of brain matter. The system includes an acoustic assembly for delivering ultrasound into a target voxel and an interferometer for delivering sample light and an optical source for frequency shifting the sample light. The interferometer combines the sample light with the background light to create an interference light pattern. The system also includes a controller for operating the acoustic assembly and interferometer in synchrony with the ultrasound pulses. The interference light patterns are detected by a detector and processed to determine the physiologically-dependent optical parameters of the target voxel, which can be used to reconstruct the amplitude of the signal light and determine neural activity within the target voxel. The technical effects of the invention include improved resolution and accuracy of brain matter imaging and the ability to measure changes in blood flow and oxygen concentration in real-time.

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 than ˜0.1 ms-1 ms) due to the scatters' motion (for example, blood flow) inside living biological tissue, but requires bulky and expensive equipment.

Another technique uses crystal-based holography to combine a reference light beam and the sample light beam into a constructive interference pattern, but can be adversely affected by rapid speckle decorrelation, since the response time of the crystal is usually much longer than the speckle correlation time.

However, the conventional CCD cameras used for heterodyne PSD have low frame rates, and therefore suffer from a relatively low speed relative to the speckle decorrelation time, thereby making this set up insufficient for in vivo deep tissue applications.

Thus, only a few bits of a pixel value can be used to represent the useful AC signal, while most of the bits are wasted in representing the DC background, resulting in a low efficiency in the use of bits.

Besides the challenges posed by the signal-to-noise ratio, speckle decorrelation time, and efficient pixel bit processing, another challenge involves obtaining sufficient axial resolution (i.e., the depth resolution or ultrasound propagation direction).

Although PW UOT improves axial resolution, the pulsed UOT signals are weak relative to continuous UOT signals.

Although the UOT schemes described above may be sufficient for certain applications, such UOT schemes are inappropriate for the application of 3D-resolved, highly sensitive detection of small signals (e.g., blood-oxygen-level dependent signals) non-invasively through thick scattering layers, such as the human skull.

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