Efficient label-free in vivo photoacoustic imaging of melanoma cells using a condensed NIR-I spectral window.

In this paper, we propose an efficient label-free in vivo photoacoustic (PA) imaging of melanoma using a condensed near infrared-I (NIR-I) supercontinuum light source. Although NIR-II spectral window is advantageous such as longer penetration depth compared to the NIR-I region, supercontinuum light sources emitting both NIR-I and NIR-II region could lower the efficiency to target melanoma because of low optical power density in the melanoma's absorption spectra. To exploit efficient in vivo PA imaging of melanoma, we demonstrated the light source emitting from visible (532-600 nm) to NIR-I (600-1000 nm) by optimizing stimulated Raman scattering induced supercontinuum generation. The melanoma's structure is successfully differentiated from blood vessels at a high pulse energy of 2.5 µJ and a flexible pulse repetition rate (PRR) of 5-50 kHz. The proposed light source with the microjoules energies and tens of kHz of PRR can potentially accelerate clinical trials such as early diagnosis of melanoma.

Nanosecond SRS fiber amplifier for label-free near-infrared photoacoustic microscopy of lipids.

Near-infrared photoacoustics receives increasing interest as an intravital modality to sense key biomolecules. One of the most central types of biomolecules of interest are lipids as they constitute essential bio-hallmarks of cardiovascular and metabolic diseases and their in-vivo detection holds insightful information about disease progression and treatment monitoring. However, the full potential of near-infrared photoacoustic for high-resolution and high-sensitivity biomedical studies of lipids has so far not been exploited due a lack of appropriate excitation sources delivering short-pulses at high-repetition-rate, high-pulse-energy, and wavelength around 1200 nm. Here, we demonstrate a custom-built SRS fiber amplifier that provides optical excitations at 1192.8 nm, repetition rates of 200 kHz, pulse durations below 2 ns, and pulse energies beyond 5 µJ. We capitalize on the performance of our excitation source and show near-infrared photoacoustics resolving intrinsic lipid contrast in biomedically relevant specimens ranging from single cells to lipid-rich tissue with subcellular resolution.

Phase stable swept-source optical coherence tomography with active mode-locking laser for contrast enhancements of retinal angiography.

Swept-source optical coherence tomography (SS-OCT) is an attractive high-speed imaging technique for retinal angiography. However, conventional swept lasers vary the cavity length of the laser mechanically to tune the output wavelength. This causes sweep-timing jitter and hence low phase stability in OCT angiography. Here, we improve an earlier phase-stabilized, akinetic, SS-OCT angiography (OCTA) method by introducing coherent averaging. We develop an active mode-locking (AML) laser as a high phase-stable akinetic swept source for the OCTA system. The phase stability of the improved system was analyzed, and the effects of coherent averaging were validated using a retina phantom. The effectiveness of the coherent averaging method was further confirmed by comparing coherently and conventionally averaged en face images of human retinal vasculature for their contrast-to-noise ratio, signal-to-noise ratio, and vasculature connectivity. The contrast-to-noise ratio was approximately 1.3 times larger when applying the coherent averaging method in the human retinal experiment. Our coherent averaging method with the high phase-stability AML laser source for OCTA provides a valuable tool for studying healthy and diseased retinas.

Linear-in-wavenumber actively-mode-locked wavelength-swept laser.

We report on an akinetic actively-mode-locked wavelength-swept laser (ASL) with a sweep that is highly linear in wavenumber. By tailoring the drive waveform of the intracavity modulator, the wavenumber sweep was further linearized to enable high fidelity frequency-domain interferometric ranging without resampling of the acquired data. Used for catheter-based optical coherence tomography, the ASL showed comparable imaging performance to a state-of-the-art polygon-based wavelength-swept source at a matching sweep rate of 103.6 kHz, a duty cycle of 95%, and a bandwidth of 100 nm, centered at 1330 nm.