Confocal photoacoustic microscopy with optical lateral resolution
US-9226666-B2 · Jan 5, 2016 · US
US10368752B1 · US · B1
| Field | Value |
|---|---|
| Publication number | US-10368752-B1 |
| Application number | US-201815988799-A |
| Country | US |
| Kind code | B1 |
| Filing date | May 24, 2018 |
| Priority date | Mar 8, 2018 |
| Publication date | Aug 6, 2019 |
| Grant date | Aug 6, 2019 |
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Disclosed herein are devices and methods for modifying a conventional imager to have functional features similar to that of a lock-in camera. Optical mask devices are configured to be coupled to conventional imager sensors and the configuration of the mask devices can be adjusted to acquire image data in rapid succession. One variation of an optical mask device comprises a substrate comprising a pattern of light-blocking and light-transmitting regions and an attachment structure for coupling the optical mask device to the imager. The substrate is configured to adjust the position of the light-blocking regions and light-transmitting regions relative to the light-sensing region of the imager based on a set of one or more predetermined substrate configurations. In some variations, the mask device and/or the imager sensor may be mechanically moved relative to each other based on the set of one or more predetermined substrate configurations.
Opening claim text (preview).
The invention claimed is: 1. A method for non-invasive optical detection of neural activity comprising: splitting a light beam into a sample light signal and a reference light signal; directing the sample light signal to a tissue sample of an anatomical structure and the reference light signal along a light path that does not interact with the tissue sample of the anatomical structure, the reference light signal configured to cycle through a plurality of phases; adjusting an optical mask device disposed over a light-sensing region of an imager to have a first pattern of light-blocking regions and light-transmitting regions; acquiring, while the optical mask has the first pattern of light-blocking regions and light-transmitting regions and while the reference light signal has a first phase included in the plurality of phases, a first set of light interference pattern data from the tissue sample at a first time point using a first set of detector pixels in the light-sensing region of the imager, the first light interference pattern data comprising a combination of the reference light signal having the first phase and the sample light signal after the sample light signal interacts with the tissue sample; adjusting the optical mask device to have a second pattern of light-blocking regions and light-transmitting regions; acquiring, while the optical mask has the second pattern of light-blocking regions and light-transmitting regions and while the reference light signal has a second phase included in the plurality of phases, a second set of light interference data from the tissue sample at a second time point using a second set of detector pixels in the light-sensing region of the imager, the second light interference pattern data comprising a combination of the reference light signal having the second phase and the sample light signal after the sample light signal interacts with the tissue sample; and calculating a first light intensity value by combining intensity values of each detector pixel in the first set of detector pixels and calculating a second light intensity value by combining intensity values of each detector pixel in the second set of detector pixels; wherein a combination of the first light intensity value and the second light intensity value represents the neural activity. 2. The method of claim 1 , wherein the detector pixels in the second set are different from the detector pixels in the first set. 3. The method of claim 1 , wherein the first phase is 0 and the second phase is π. 4. The method of claim 1 , further comprising determining a physiological optical parameter of the tissue sample based on the first and second light intensity values. 5. The method of claim 4 , wherein the physiological optical parameter is a level of deoxygenated and/or oxygenated hemoglobin concentration of relative abundance. 6. The method of claim 4 , wherein the physiological optical parameter is a level of neuronal movement or activity of the tissue sample. 7. The method of claim 1 , wherein the sample light signal is frequency encoded. 8. The method of claim 7 , where the sample light signal is frequency encoded using ultrasound pulses delivered to the tissue sample. 9. The method of claim 1 , wherein the sample light signal is path length encoded. 10. The method of 1 , further comprising: adjusting the optical mask to have a third pattern of light-blocking regions and light-transmitting regions; acquiring, while the optical mask has the third pattern of light-blocking regions and light-transmitting regions and while the reference light signal has a third phase included in the plurality of phases, a third set of light interference data from the tissue sample at a third time point using a third set of detector pixels in the light-sensing region of the imager, wherein the third light interference pattern data comprises a combination of the reference light signal having the third phase and the sample light signal after the sample light signal interacts with the tissue sample; adjusting the optical mask to have a fourth pattern of light-blocking regions and light-transmitting regions; acquiring, while the optical mask has the fourth pattern of light-blocking regions and light-transmitting regions and while the reference light signal has a fourth phase included in the plurality of phases, a fourth set of light interference data from the tissue sample at a fourth time point using a fourth set of detector pixels in the light-sensing region of the imager, wherein the fourth light interference pattern data comprises a combination of the reference light signal having the fourth phase and the sample light signal after the sample light signal interacts with the tissue sample; and calculating a third light intensity value by combining intensity values of each detector pixel in the third set of detector pixels and calculating a fourth light intensity value by combining intensity values of each detector pixel in the fourth set of detector pixels. 11. The method of claim 10 , wherein the first phase is 0, the second phase is π/2, the third phase is π, and the fourth phase is 3π/2, wherein the method further comprises determining a physiological optical parameter of the tissue sample based on the first, second, third, and fourth light intensity values. 12. A method for non-invasive optical measurement of neural activity comprising: splitting a light beam into a sample light signal and a reference light signal; directing the sample light signal to a tissue sample of an anatomical structure and the reference light signal along a light path that does not interact with the tissue sample of the anatomical structure, the reference light signal configured to cycle through a predetermined number (N) of phases; adjusting positions of light-blocking and light-transmitting regions of an optical mask at a predetermined number (X) of time points to a plurality of predetermined positions that correspond with the predetermined number (N) of phases of the reference light signal, wherein the optical mask is disposed over a detector pixel array of an imager; acquiring light interference data for each of the plurality of predetermined positions using the detector pixel array; and calculating a plurality (X) of light intensity values corresponding to the predetermined number (N) of phases of the reference light signal by averaging imager detector pixel values for each of the predetermined number (X) of time points, wherein changes in the plurality of light intensity values over time represent neural activity.
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