Fluorescence-informed photoacoustic discrimination of multiple chromophores by lifetime mapping optically gated responses.

Synchronously Amplified Photoacoustic Image Recovery (SAPhIRe) offers improved background suppression using non-linear properties of modulatable contrast agents. Using SAPhIRe, multiple contrast agents in the same absorption window can be detected independently based on their unique triplet-state lifetimes. Here, we have demonstrated the unmixing of rose bengal and eosin Y signals from solution based on triplet-state lifetime mapping using both fluorescence and photoacoustics. Varying the pump-probe delay enables resolution and recovery of fast-decaying rose bengal and of slowly decaying eosin Y modulated photoacoustic signals, resulting from optically gated triplet state residence. Distinct images were reconstructed within tissue-mimicking phantom using the fitting coefficients of triplet-state lifetimes. Fluorescence was used to screen for modulation prior to photoacoustic imaging. The results suggest that lifetime unmixing can be utilized to simultaneously detect multiple pathologies with overlapping spectra using photoacoustic imaging.

Synchronously Amplified Photoacoustic Image Recovery (SAPhIRe).

In molecular and cellular photoacoustic imaging with exogenous contrast agents, image contrast is plagued by background resulting from endogenous absorbers in tissue. By using optically modulatable nanoparticles, we develop ultra-sensitive photoacoustic imaging by rejecting endogenous background signals and drastically improving signal contrast through time-delayed pump-probe pulsed laser illumination. Gated by prior pump excitation, modulatable photoacoustic (mPA) signals are recovered from unmodulatable background through simple, real-time image processing to yield background-free photoacoustic signal recovery within tissue mimicking phantoms and from ex-vivo tissues. Inherently multimodal, the fluorescence and mPA sensitivity improvements demonstrate the promise of Synchronously Amplified Photoacoustic Image Recovery (SAPhIRe) for PA imaging in diagnosis and therapy.

Integrated optical coherence tomography and multielement ultrasound transducer probe for shear wave elasticity imaging of moving tissues.

Accurate measurements of microelastic properties of soft tissues in-vivo using optical coherence elastography can be affected by motion artifacts caused by cardiac and respiratory cycles. This problem can be overcome using a multielement ultrasound transducer probe where each ultrasound transducer is capable of generating acoustic radiation force (ARF) and, therefore, creating shear waves in tissue. These shear waves, produced during the phase of cardiac and respiratory cycles when tissues are effectively stationary, are detected at the same observation point using phase-sensitive optical coherence tomography (psOCT). Given the known distance between the ultrasound transducers, the speed of shear wave propagation can be calculated by measuring the difference between arrival times of shear waves. The combined multitransducer ARF/psOCT probe has been designed and tested in phantoms and ex-vivo studies using fresh rabbit heart. The measured values of shear moduli are in good agreement with those reported in literature. Our results suggest that the developed multitransducer ARF/psOCT probe can be useful for many in-vivo applications, including quantifying the microelasticity of cardiac muscle.

Optimization of dual-wavelength intravascular photoacoustic imaging of atherosclerotic plaques using Monte Carlo optical modeling.

Coronary heart disease (the presence of coronary atherosclerotic plaques) is a significant health problem in the industrialized world. A clinical method to accurately visualize and characterize atherosclerotic plaques is needed. Intravascular photoacoustic (IVPA) imaging is being developed to fill this role, but questions remain regarding optimal imaging wavelengths. We utilized a Monte Carlo optical model to simulate IVPA excitation in coronary tissues, identifying optimal wavelengths for plaque characterization. Near-infrared wavelengths (≤1800 nm) were simulated, and single- and dual-wavelength data were analyzed for accuracy of plaque characterization. Results indicate light penetration is best in the range of 1050 to 1370 nm, where 5% residual fluence can be achieved at clinically relevant depths of ≥2 mm in arteries. Across the arterial wall, fluence may vary by over 10-fold, confounding plaque characterization. For single-wavelength results, plaque segmentation accuracy peaked at 1210 and 1720 nm, though correlation was poor (<0.13). Dual-wavelength analysis proved promising, with 1210 nm as the most successful primary wavelength (≈1.0). Results suggest that, without flushing the luminal blood, a primary and secondary wavelength near 1210 and 1350 nm, respectively, may offer the best implementation of dual-wavelength IVPA imaging. These findings could guide the development of a cost-effective clinical system by highlighting optimal wavelengths and improving plaque characterization.

Real-Time Intravascular Ultrasound and Photoacoustic Imaging.

Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging is an emerging hybrid modality being explored as a means of improving the characterization of atherosclerotic plaque anatomical and compositional features. While initial demonstrations of the technique have been encouraging, they have been limited by catheter rotation and data acquisition, displaying, and processing rates on the order of several seconds per frame as well as the use of off-line image processing. Herein, we present a complete IVUS/IVPA imaging system and method capable of real-time IVUS/IVPA imaging, with online data acquisition, image processing, and display of both IVUS and IVPA images. The integrated IVUS/IVPA catheter is fully contained within a 1-mm outer diameter torque cable coupled on the proximal end to a custom-designed spindle enabling optical and electrical coupling to system hardware, including a nanosecond-pulsed laser with a controllable pulse repetition frequency capable of greater than 10 kHz, motor and servo drive, a US pulser/receiver, and a 200-MHz digitizer. The system performance is characterized and demonstrated on a vessel-mimicking phantom with an embedded coronary stent intended to provide IVPA contrast within content of an IVUS image.

Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm.

Recently, a dual photoacoustic and ultrasound contrast agent-named photoacoustic nanodroplet-has been introduced. Photoacoustic nanodroplets consist of a perfluorocarbon core, surfactant shell, and encapsulated photoabsorber. Upon pulsed laser irradiation the perfluorocarbon converts to gas, inducing a photoacoustic signal from vaporization and subsequent ultrasound contrast from the resulting gas microbubbles. In this work we synthesize nanodroplets which encapsulate gold nanorods with a peak absorption near 1064 nm. Such nanodroplets are optimal for extended photoacoustic imaging depth and contrast, safety and system cost. We characterized the nanodroplets for optical absorption, image contrast and vaporization threshold. We then imaged the particles in an ex vivo porcine tissue sample, reporting contrast enhancement in a biological environment. These 1064 nm triggerable photoacoustic nanodroplets are a robust biomedical tool to enhance image contrast at clinically relevant depths.