Abstract: The present invention relates to systems for low-energy (e.g., 1.0 nJ-7.0 nJ) photoacoustic microscopy and methods for employing such systems. In certain embodiments, such systems employ a low-energy nanosecond pulsed laser beam (NPLB), at least two amplifiers, and a data acquisition system with at least three channels to generate at least three digital signals (e.g., which are averaged and normalized to the energy of the NPLB). In other embodiments, provided herein are systems for combined use of photoacoustic microscopy, dye-based microscopy (e.g., with fluorescein), and optical coherence tomography.

Abstract: A laser whose emission is modulated by ultrasound is presented. The laser is usually micron-sized. In response to ultrasound modulation, the laser emission increases and decreases. Such a change in emission can be detected by external optical detectors. This type of laser can be used as a new type of imaging modality, in which laser emission in combination with sound waves or ultrasound waves, is used for imaging Laser emission has a much narrower spectral linewidth and stronger intensity than fluorescence and therefore is able to achieve higher sensitivity, whereas sound waves are used to provide a better spatial resolution of the laser emission from the laser. In ultrasound modulated laser based imaging, multiple lasers can be placed inside cells or tissues.

Abstract: A method of removing microvessels includes applying a burst of acoustic energy at a target location, applying a pulse of optical energy at the target location, and promoting cavitation at the target location by synchronizing an arrival of the burst of acoustic energy and the optical energy at the target location. The burst of acoustic energy has a pressure below 5.0 MPa. The pulse of optical energy at the target location has a fluence less than 100 mJ/cm2. At least a portion of the pulse is concurrent with the burst and the optical energy has an optical area that is overlapping with an acoustic area of the acoustic energy at the target location.

Abstract: An imaging system for cell-based therapies is provided. The imagining system includes one or more optical tags configured for insertion into a cell or biological tissue, an excitation light source configured to illuminate the one or more optical tags; a detector configured to measure optical emission of the one or more optical tags; an imaging subsystem configured to determine a three-dimensional location of each of the one or more optical tags in the cell or biological tissue; and a controller in electrical communication with the excitation light source, the detector, and the imaging subsystem. Each of the one or more optical tags has a contrasting feature and includes a fluorescent material. The contrasting feature may be defined by at least one of a refractive index, shape, color, and laser emission of each optical tag of the one or more optical tags.

Abstract: A method of removing microvessels includes applying a burst of acoustic energy at a target location, applying a pulse of optical energy at the target location, and promoting cavitation at the target location. The burst of acoustic energy has a pressure below 5.0 MPa. The pulse of optical energy at the target location has a fluence less than 100 mJ/cm2. At least a portion of the pulse is concurrent with the burst and the optical energy has an optical area that is overlapping with an acoustic area of the acoustic energy at the target location.

Abstract: A method and system for performing online adapted radiotherapy are provided using combined ultrasound and ionizing radiation induced acoustic imaging (iRAI) computed tomography imaging techniques that can be used for measurement of low to ultrahigh dose deliveries (>40 Gy/s). Multiplexed transducers detect US and iRAI signals allowing for anatomical/functional imaging and radiation mapping with absolute dosimetry measurements of a region of interest during a radiotherapy session. Corrections to radiation dosage intensities and locations is determined and provided as feedback to a radiation source to improve the accuracy of applied radiation dosages intra- or inter-radiotherapy treatment sessions preventing the irradiation of healthy tissues and ensuring the accurate delivery of radiation to a tumor or region of interest.

Abstract: A laser whose emission is modulated by ultrasound is presented. The laser is usually micron-sized. In response to ultra-sound modulation, the laser emission increases and decreases. Such a change in emission can be detected by external optical detectors. This type of laser can be used as a new type of imaging modality, in which laser emission in combination with sound waves or ultra-sound waves, is used for imaging Laser emission has a much narrower spectral linewidth and stronger intensity than fluorescence and therefore is able to achieve higher sensitivity, whereas sound waves are used to provide a better spatial resolution of the laser emission from the laser. In ultrasound modulated laser based imaging, multiple lasers can be placed inside cells or tissues.

Abstract: The present invention relates to systems for low-energy (e.g., 1.0 nJ-7.0 nJ) photoacoustic microscopy and methods for employing such systems. In certain embodiments, such systems employ a low-energy nanosecond pulsed laser beam (NPLB), at least two amplifiers, and a data acquisition system with at least three channels to generate at least three digital signals (e.g., which are averaged and normalized to the energy of the NPLB). In other embodiments, provided herein are systems for combined use of photoacoustic microscopy, dye-based microscopy (e.g., with fluorescein), and optical coherence tomography.

Abstract: A method of performing a photoacoustic physio-chemical analysis is provided. The method includes performing one or more photoacoustic scans on a tissue to generate a plurality of photoacoustic signals. The photoacoustic signals are transformed into a frequency domain to form a power spectra. The method also includes generating a two dimensional (2D) physio-chemical spectrogram from the power spectra. A probe for performing a photoacoustic physio-chemical analysis is also provided.

Abstract: A method of removing microvessels includes applying a burst of acoustic energy at a target location, applying a pulse of optical energy at the target location, and promoting cavitation at the target location. The burst of acoustic energy has a pressure below 5.0 MPa. The pulse of optical energy at the target location has a fluence less than 100 mJ/cm2. At least a portion of the pulse is concurrent with the burst and the optical energy has an optical area that is overlapping with an acoustic area of the acoustic energy at the target location.

Abstract: A method of performing a photoacoustic physio-chemical analysis is provided. The method includes performing one or more photoacoustic scans on a tissue to generate a plurality of photoacoustic signals. The photoacoustic signals are transformed into a frequency domain to form a power spectra. The method also includes generating a two dimensional (2D) physio-chemical spectrogram from the power spectra. A probe for performing a photoacoustic physio-chemical analysis is also provided.

Abstract: Provided herein are microcrystalline forms of drugs. In particular, provided herein are microcrystalline drug formulations for delivery to macrophages and treatment of disease.

Abstract: A system and method for monitoring laser therapy of a target tissue include a therapeutic control unit having a first light source configured to deliver light to the target tissue for therapy, an ultrasonic transducer for receiving photoacoustic signals generated due to optical absorption of light energy by the target tissue, and a monitoring control unit in communication with the ultrasonic transducer for reconstructing photoacoustic tomographic images from the received photoacoustic signals to provide an optical energy deposition map of the target tissue. A second light source utilized for imaging may also be provided.

Abstract: A system and method for spectroscopic photoacoustic tomography of a sample include at least one light source configured to deliver light pulses at two or more different wavelengths to the sample. An ultrasonic transducer is disposed adjacent to the sample for receiving photoacoustic signals generated due to optical absorption of the light pulses by the sample. A control system is provided in communication with the ultrasonic transducer for reconstructing photoacoustic tomographic images from the received photoacoustic signals, wherein upon application of light pulses of two or more different wavelengths to the sample, the control system is configured to determine the local spectroscopic absorption of substances at any location in the sample. The system may further provide for one or more of ultrasound imaging. Doppler ultrasound imaging, and diffuse optical imaging of the sample.

Abstract: A system and method for monitoring photodynamic therapy of a target tissue, where the target tissue contains a photosensitizing substance, include a first light source configured to deliver light to the target tissue, the first light source having a wavelength capable of exciting the photosensitizing substance. An ultrasonic transducer receives photoacoustic signals generated due to optical absorption of light energy by the target tissue, and a control unit in communication with the ultrasonic transducer reconstructs photoacoustic tomographic images from the received photoacoustic signals to provide an indication of optical energy deposition due to the photosensitizing substance in the target tissue.

Abstract: A system and method for photoacoustic tomography of a sample, such as a mammalian joint, includes a light source configured to deliver light to the sample, an ultrasonic transducer disposed adjacent to the sample for receiving photoacoustic signals generated due to optical absorption of the light by the sample, a motor operably connected to at least one of the sample and the ultrasonic transducer for varying a position of the sample and the ultrasonic transducer with respect to one another along a scanning path, and a control system in communication with the light source, the ultrasonic transducer, and the motor for reconstructing photoacoustic images of the sample from the received photoacoustic signals.

Abstract: A system and method for photoacoustic guided diffuse optical imaging of a sample include at least one light source configured to deliver light to the sample, at least one ultrasonic transducer disposed adjacent to the sample for receiving photoacoustic signals generated due to optical absorption of the light by the sample, and at least one optical detector for receiving optical signals generated due to light scattered by the sample. A control system is provided in communication with the at least one light source, the ultrasonic transducer, and the optical detector for reconstructing photoacoustic images of the sample from the received photoacoustic signals and reconstructing optical images of the sample from the received optical signals. The priori anatomical information and spatially distributed optical parameters of biological tissues from the photoacoustic images employed in diffuse optical imaging may improve the accuracy of measurements and the reconstruction speed.