Deep tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light

An apparatus for irradiating a scattering medium, comprising:

• (a) an ultrasound transducer for transmitting ultrasound waves to one or more foci in one or more regions of a scattering medium;
• (b) a laser for transmitting input light to the one or more foci, wherein the ultrasound waves at least partially frequency shift the input light into modulated light as the modulated light passes through the foci concurrently with the ultrasound waves;
• (c) a Digital Optical Phase Conjugation (DOPC) device, comprising a digital programmable spatial light modulator (SLM) connected to and imaged onto a digital camera, wherein:
• (i) the camera:
• is positioned to collect a portion of the modulated light that has exited the scattering medium, as collected modulated light, and
• outputs one or more digital signals in response thereto;
• (ii) a computer connected to the DOPC device calculates one or more phases of the collected modulated light using the digital signals;
• (iii) a computer connected to the DOPC device computes phase conjugate phases that are phase conjugates of the phases of the collected modulated light;
• (iv) the DOPC device irradiates the scattering medium with time reversed fields having the phase conjugate phases, wherein the time reversed fields include a desired component that converges back to the foci, and a background component due to incomplete time reversal resulting from only the portion of the modulated light being collected;
• (v) a computer connected to the DOPC device phase shifts one or more of the phase conjugate phases by one or more amounts to remove the desired component that converges to the foci, to produce one or more background fields that at least approximate the background component;
• (vi) the SLM is programmed and positioned to sequentially modulate light to form first the light comprising time reversed fields and then the light comprising the background fields;
• (d) a detector, wherein:
• the detector detects fluorescence transmitted from the scattering medium in response to the time reversed fields, to produce a first detected signal, and
• the detector detects fluorescence transmitted from the scattering medium in response to the background fields, to produce a second detected signal, and
• (e) a computer connected to the detector, wherein the computer subtracts the second detected signal from the first detected signal, to obtain an output that at least approximates an interaction between a complete time reversed light field, comprising phase conjugates of all of the modulated light's fields, and the scattering medium.

A method of fabricating an apparatus for irradiating a scattering medium, comprising:

• (a) providing, positioning, or providing and positioning, a source of one or more signals, such that the source transmits the one or more signals to one or more regions of a scattering medium;
• (b) providing, positioning, or providing and positioning, a laser, such that the laser transmits input electromagnetic (EM) radiation through the one or more regions of the scattering medium concurrently with the one or more signals, wherein the one or more signals at least partially modulate the input EM radiation into modulated radiation;
• (c) providing, positioning, or providing and positioning, a Digital Optical Phase Conjugation (DOPC) device such that the DOPC device collects at least a portion of the modulated radiation, that has exited the scattering medium, as collected modulated radiation;
• and
• (d) providing, connecting, or providing and connecting, one or more computers, such that the one or more computers:
• (i) receive a phase map of the collected modulated radiation,
• (ii) digitally phase conjugate the phase map to produce a phase conjugate map,
• (iii) digitally modify the phase conjugate map to produce a digitally modified phase map used to produce one or more background fields that at least approximate a background component, the background component resulting from incomplete time reversal of the modulated radiation, and the incomplete time reversal resulting from only the portion of the modulated radiation being collected;
• (iv) output the phase conjugate map and the digitally modified phase map to the DOPC device;
• and wherein the DOPC device:
• produces first EM radiation using the phase conjugate map, the first EM radiation including the background component and a desired component comprising time reversed EM radiation that converges back to the one or more regions, and the first EM radiation irradiating and interacting with the scattering medium to produce a first detected signal, and
• produces second EM radiation comprising the one or more background fields, using the digitally modified phase map, the second EM radiation irradiating and interacting with the scattering medium to produce a second detected signal;
• and
• the one or more computers subtract the second detected signal from the first detected signal to obtain an output that at least approximates an interaction between complete time reversed EM radiation, obtained by phase conjugating all the modulated radiation, and the scattering medium.

A method of irradiating a scattering medium, comprising:

• receiving a phase map of a portion of modulated radiation, wherein the portion of the modulated radiation was obtained from a process comprising:
• (i) modulating electromagnetic (EM) radiation with a signal, in a region of a scattering medium, to form the modulated radiation;
• (ii) collecting the portion of the modulated radiation in a digital optical phase conjugation (DOPC) device;
• and
• (iii) measuring the phase map of the portion of the modulated radiation;
• digitally phase conjugating the phase map to produce a phase conjugate map;
• digitally modifying the phase conjugate map to produce a digitally modified phase map used to produce one or more background fields that at least approximate a background component, the background component resulting from incomplete time reversal of the modulated radiation, and the incomplete time reversal resulting from only the portion of the modulated radiation being collected;
• outputting the phase conjugate map and the digitally modified phase map to the DOPC device;
• receiving a first detected signal and a second detected signal, wherein:
• the first detected signal was formed using a process comprising:
• producing first EM radiation, in the DOPC device, using the phase conjugate map, the first EM radiation including the background component and a desired component comprising time reversed EM radiation that converges back to the region, and the first EM radiation irradiating and interacting with the scattering medium to produce the first detected signal;
• and
• the second detected signal was formed using a process comprising:
• producing second EM radiation comprising the one or more background fields, in the DOPC device and using the digitally modified phase map, the second EM radiation irradiating and interacting with the scattering medium to produce the second detected signal;
• subtracting the second detected signal from the first detected signal to obtain an output that at least approximates an interaction between complete time reversed EM radiation, obtained by phase conjugating all the modulated radiation, and the scattering medium.