Kevan Bell

Non-interferometric photoacoustic remote sensing microscopy

Elasto-optical refractive index modulation due to photoacoustic initial pressure transients produced significant reflection of a probe beam when the absorbing interface had an appreciable refractive index difference. This effect was harnessed in a new form of non-contact optical resolution photoacoustic microscopy called photoacoustic remote sensing microscopy. A non-interferometric system architecture with a low-coherence probe beam precludes detection of surface oscillations and other phase-modulation phenomenon. The probe beam was confocal with a scanned excitation beam to ensure detection of initial pressure-induced intensity reflections at the subsurface origin where pressures are largest. Phantom studies confirmed signal dependence on optical absorption, index contrast and excitation fluence. In vivo imaging of superficial microvasculature and melanoma tumors was demonstrated with ~2.7±0.5 μm lateral resolution.

Non-interferometric deep optical resolution photoacoustic remote sensing microscopy (Conference Presentation)

A novel all-optical non-contact photoacoustic microscopy system is introduced. The confocal configuration is used to ensure detection of initial pressure shock wave-induced intensity reflections at the subsurface origin where pressures are largest. Phantom studies confirm signal dependence on optical absorption, index-contrast, and excitation fluence. Taking advantage of a focused1310 nm interrogation beam, the penetration depth of the system is improved to ~ 2mm for an optical resolution system. High signal-to-noise ratios (>60dB) with ~ 2.5 cm working distance from the objective lens to the sample is achieved. Real-time in-vivo imaging of microvasculature and melanoma tumors are demonstrated.

Integrated transrectal probe for translational ultrasound-photoacoustic imaging

A compact photoacoustic transrectal probe is constructed for improved imaging in brachytherapy treatment. A 192 element 5 MHz linear transducer array is mounted inside a small 3D printed casing along with an array of optical fibers. The device is fed by a pump laser and tunable NIR-optical parametric oscillator with data collected by a Verasonics ultrasound platform. This assembly demonstrates improved imaging of brachytherapy seeds in phantoms with depths up to 5 cm. The tuneable excitation in combination with standard US integration provides adjustable contrast between the brachytherapy seeds, blood filled tubes and background tissue.

Coherence-gated photoacoustic remote sensing microscopy (Conference Presentation)

Photoacoustic remote sensing (PARS) microscopy is a novel photoacoustic modality which provides non-contact reflection-mode operation within optical penetration regimes. It has thus far demonstrated exceptional in vivo imaging capabilities with high signal-to-noise (greater than 70dB) and sub-cellular lateral resolution (on the order of 600 nm). Moreover, being non-contact opens a wide range of previously inaccessible imaging targets where acoustic coupling to the sample is impractical. One disadvantage of the technique however is the lack of time-gated depth discrimination which has long been a staple of more conventional photoacoustic methods. Rather, depth-resolving ability has been solely defined by the optical section provided by the primary objective lens. Here a pulsed short-wave infrared low-coherence detection beam in a spectral-domain OCT system is used to probe depth-resolved reflectivity before and immediately after visible pulsed excitation. A difference image between these A-scans reveals signals with optical absorption contrast. Simulations based on recently-developed time-domain modeling of low-coherence PARS reflectivity changes is used to generate software-phantom images. We used a 1310-nm ns-pulsed interrogation source with 45nm linewidth, along with a 532-nm ns-pulsed excitation beam. The effects of various material and apparatus parameters are discussed along with extensive analytical and simulation results. These showcase the potential capabilities of the approach, such as depth resolved spectral unmixing (with oxygen saturation) and discrimination of blood vessels in highly scattering media, along with foreseeable limitations and potential implementation issues.

Toward wide-field high-speed photoacoustic remote sensing microscopy

Optical imaging modalities are commonly characterized by rapid acquisition rates, enabling real-time feedback. Photoacoustic Remote Sensing (PARS) microscopy takes advantage of intensity reflectivity modulations induced through large photoacoustic initial pressures to provide optical absorption imaging contrast. The PARS signals are characterized by short time-domain behavior independent of time-gated effects such as acoustic propagation to a detector. Here, improved imaging rates are demonstrated. This is accomplished by introducing an analog peak detection circuit, which reduces data bandwidth requirements, and by employing a high repetition rate fiber laser. These additions enable voxel scan rates in the megahertz range. High quality real-time captures, orders of magnitude faster than previous PARS systems, are presented.

Scattering cross-sectional modulation in photoacoustic remote sensing microscopy

Modeling and observations of large scattering cross-sectional modulations in absorbing optical scatterers due to a pulsed laser excitation are reported. Rapid laser-induced thermo-elastic expansion produces nontrivial perturbations to the local refractive indices. This mechanism forms the basis of a recent non-contact photoacoustic technique known as photoacoustic remote sensing microscopy. A time-evolution model is constructed and discussed, comparing it with existing planar models, time-independent models, and experiments. Fractional scattering cross-sectional modulations greater than 20 times that of the unperturbed particles are predicted and observed for the first time, to the best of our knowledge. A nonlinear acoustic enlargement effect is likewise predicted and observed. Implications of system and material properties are explored.

Temporal evolution of low-coherence reflectometry signals in photoacoustic remote sensing microscopy (Conference Presentation)

We recently discovered that strong reflectivity modulations occur when a pulsed laser excites an absorption interface with an existing refractive index contrast. These modulations are observed using a low-coherence interrogation beam co-focused and co-scanned with an excitation beam to form high-resolution all-optical photoacoustic images. We call this new form of microscopy Photoacoustic Remote Sensing (PARS). To better understand the mechanism, analytical models were created of the time-evolution of these PARS signals. Shock waves propagating from the absorption interface create refractive index steps that form a time-varying multi-layer etalon. Besides an initial-pressure reflectivity change, GHz-modulations are predicted due to the propagating etalon effect. The characteristics of these modulations are related to the optical coherence length of the probe beam and the intrinsic optical properties of the sample. 1D plane-wave and 3D Mie-theory-based analytical models are compared with finite-difference time-domain simulations and experiments involving phantoms with different absorption- and refractive-index interfaces. Experimentally-observed modulations are detected with extremely high signal-to-noise ratios in phantoms and animal models. The newly predicted modulation mechanism offers a promising signature for deep all-optical absorption-contrast imaging with high fidelity.

Photoacoustic remote sensing microscopy with lock-in amplification

High sensitive detection with lock-in amplification can provide high signal noise ratio even when noise is in orders of magnitude higher than the signal. Here we report to combine lock-in amplification with a novel photoacoustic remote sensing (PARS) technology to achieve high resolution, high contrast, all optical non-contact photoacoustic imaging at depth beyond optical scattering limitation. We demonstrate phantom measurements from PARS with lock-in technology were several orders of magnitude more sensitive than those from PARS with the broadband detection techniques.

Temporal evolution of low-coherence reflectrometry signals in photoacoustic remote sensing microscopy

Recently, a new noncontact reflection-mode imaging modality called photoacoustic remote sensing (PARS) microscopy was introduced providing optical absorption contrast. Unlike previous modalities, which rely on interferometric detection of a probe beam to measure surface oscillations, the PARS technique detects photoacoustic initial pressures induced by a pulsed laser at their origin by monitoring intensity modulations of a reflected probe beam. In this paper, a model describing the temporal evolution from a finite excitation pulse is developed with consideration given to the coherence length of the interrogation beam. Analytical models are compared with approximations, finite-difference time-domain (FDTD) simulations, and experiments with good agreement.

Multi-scale photoacoustic remote sensing (PARS)(Conference Presentation)

We introduce a novel multi-scale photoacoustic remote sensing (PARS) imaging system. Our system can provide optical resolution details for superficial structures as well as acoustic resolution for deep-tissue imaging down to 5 cm, in a non-contact setting. PARS system does not require any contact with the sample or ultrasound coupling medium. The optical resolution PARS (OR-OARS) system uses optically focused pulsed excitation with optical detection of photoacoustic signatures using a long-coherence interrogation beam co-focused and co-scanned with the excitation spot. In the OR-PARS initial pressures are sampled right at their subsurface origin where acoustic pressures are largest. The Acoustic resolution PARS (AR-PARS) picks up the surface oscillation of the tissue caused by generated photoacoustic signal using a modified version of Michelson interferometry. By taking advantage of 4-meters polarization maintaining single-mode fiber and a green fiber laser we have generated a multi-wavelength source using stimulated Raman scattering. Remote functional imaging using this multi-wavelength excitation source and PARS detection mechanism has been demonstrated. The oxygen saturation estimations are shown for both phantom and in vivo studies. Images of blood vessel structures for an In vivo chicken embryo model is demonstrated. The Phantom studies indicates ~3µm and ~300µm lateral resolution for OR-PARS and AR-PARS respectively. To the best of our knowledge this is the first dual modality non-contact optical and acoustic resolution system used for in vivo imaging.