Lipid deposition inside the arterial wall is a key indicator of plaque vulnerability. An intravascular photoacoustic (IVPA) catheter is considered a promising device for quantifying the amount of lipid inside the arterial wall. Thus far, IVPA systems suffered from slow imaging speed (~50 s per frame) due to the lack of a suitable laser source for high-speed excitation of molecular overtone vibrations. Here, we report an improvement in IVPA imaging speed by two orders of magnitude, to 1.0 s per frame, enabled by a custom-built, 2-kHz master oscillator power amplifier (MOPA)-pumped, barium nitrite [Ba(NO3)2] Raman laser. This advancement narrows the gap in translating the IVPA technology to the clinical setting.

Confronted with the severe situation that the pace of resistance acquisition is faster than the clinical introduction of new antibiotics, health organizations are calling for effective approaches to combat methicillin‐resistant Staphylococcus aureus (MRSA) infections. Here, an approach to treat MRSA through photolysis of staphyloxanthin, an antioxidant residing in the microdomain of S. aureus membrane, is reported. This photochemistry process is uncovered through transient absorption imaging and quantitated by absorption spectroscopy, Raman spectroscopy, and mass spectrometry. Photolysis of staphyloxanthin transiently elevates the membrane permeability and renders MRSA highly susceptible to hydrogen peroxide attack. Consequently, staphyloxanthin photolysis by low‐level 460 nm light eradicates MRSA synergistically with hydrogen peroxide and other reactive oxygen species. The effectiveness of this synergistic therapy is well validated in MRSA planktonic culture, MRSA‐infected macrophage cells, stationary‐phase MRSA, persisters, S. aureus biofilms, and two mice wound infection models. Collectively, the work demonstrates that staphyloxanthin photolysis is a new therapeutic platform to treat MRSA infections.

A highly sensitive catheter probe is critical to catheter-based intravascular photoacoustic imaging. Here, we present a photoacoustic catheter probe design on the basis of collinear alignment of the incident optical wave and the photoacoustically generated sound wave within a miniature catheter housing for the first time. Such collinear catheter design with an outer diameter of 1.6 mm provided highly efficient overlap between optical and acoustic waves over an imaging depth of >6 mm in D2O medium. Intravascular photoacoustic imaging of lipid-laden atherosclerotic plaque and perivascular fat was demonstrated, where a lab-built 500 Hz optical parametric oscillator outputting nanosecond optical pulses at a wavelength of 1.7 μm was used for overtone excitation of C-H bonds. In addition to intravascular imaging, the presented catheter design will benefit other photoacoustic applications such as needle-based intramuscular imaging.

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Intravascular photoacoustic-ultrasound (IVPA-US) imaging is an emerging hybrid modality for the detection of lipid-laden plaques, as it provides simultaneous morphological and lipid-specific chemical information of an artery wall. Real-time imaging and display at video-rate speed are critical for clinical utility of the IVPA-US imaging technology. Here, we demonstrate a portable IVPA-US system capable of imaging at up to 25 frames per second in real-time display mode. This unprecedented imaging speed was achieved by concurrent innovations in excitation laser source, rotary joint assembly, 1 mm IVPA-US catheter size, differentiated A-line strategy, and real-time image processing and display algorithms. Spatial resolution, chemical specificity, and capability for imaging highly dynamic objects were evaluated by phantoms to characterize system performance. An imaging speed of 16 frames per second was determined to be adequate to suppress motion artifacts from cardiac pulsation for in vivo applications. The translational capability of this system for the detection of lipid-laden plaques was validated by ex vivo imaging of an atherosclerotic human coronary artery at 16 frames per second, which showed strong correlation to gold-standard histopathology. Thus, this high-speed IVPA-US imaging system presents significant advances in the translational intravascular and other endoscopic applications.

Intravascular photoacoustic tomography is an emerging technology for mapping lipid deposition within an arterial wall for the investigation of the vulnerability of atherosclerotic plaques to rupture. By converting localized laser absorption in lipid-rich biological tissue into ultrasonic waves through thermoelastic expansion, intravascular photoacoustic tomography is uniquely capable of imaging the entire arterial wall with chemical selectivity and depth resolution. However, technical challenges, including an imaging catheter with sufficient sensitivity and depth and a functional sheath material without significant signal attenuation and artifact generation for both photoacoustics and ultrasound, have prevented in vivo application of intravascular photoacoustic imaging for clinical translation. Here, we present a highly sensitive quasi-collinear dual-mode photoacoustic/ultrasound catheter with elaborately selected sheath material, and demonstrated the performance of our intravascular photoacoustic tomography system by in vivo imaging of lipid distribution in rabbit aortas under clinically relevant conditions at imaging speeds up to 16 frames per second. Ex vivo evaluation of fresh human coronary arteries further confirmed the performance of our imaging system for accurate lipid localization and quantification of the entire arterial wall, indicating its clinical significance and translational capability.

The quantized vibration of chemical bonds provides a way of detecting specific molecules in a complex tissue environment. Unlike pure optical methods, for which imaging depth is limited to a few hundred micrometers by significant optical scattering, photoacoustic detection of vibrational absorption breaks through the optical diffusion limit by taking advantage of diffused photons and weak acoustic scattering. Key features of this method include both high scalability of imaging depth from a few millimeters to a few centimeters and chemical bond selectivity as a novel contrast mechanism for photoacoustic imaging. Its biomedical applications spans detection of white matter loss and regeneration, assessment of breast tumor margins, and diagnosis of vulnerable atherosclerotic plaques. This review provides an overview of the recent advances made in vibration-based photoacoustic imaging and various biomedical applications enabled by this new technology.

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