Parsin Hajireza

Label-free in vivo fiber-based optical-resolution photoacoustic microscopy.

In this Letter, the capability of label-free fiber-based optical-resolution photoacoustic microscopy is demonstrated. This real-time imaging system takes advantage of image-guide fibers and a unique fiber laser. The 800 μm image-guide consists of 30,000 individual single-mode fibers in a bundle and the diode-pumped, pulsed Ytterbium fiber laser is utilized to perform up to 600 kHz repetition rate. Phantom studies indicate 7 μm resolution. The proposed setup keeps many of the powerful properties of previous tabletop OR-PAM systems, but also offers a submillimeter probe footprint and high flexibility due to the nature of the image-guide. This system could have significant clinical impact for endoscopic applications where the thin fiber can be inserted into the body.

Real-time handheld optical-resolution photoacoustic microscopy.

In this paper a new generation of optical-resolution photoacoustic microscopy (OR-PAM) with a wide range of potential clinical applications is demonstrated. Using fast scanning mirrors, an image guide with 30,000 fiber pixels, a refocusing lens and a unique probe we managed to reduce the footprint of an OR-PAM system from a stationary table-top system to a portable, 4 cm by 6 cm, probe weighing ~500 g tethered to a scanning unit. The phantom studies show that the handheld optical-resolution photoacoustic microscope is able to image with ~7 μm resolution. For in vivo studies images of the microvasculature in a Swiss Webster mouse ear are shown. The compact, flexible nature of the proposed design and the small footprint of the apparatus increase the usability of OR-PAM for potential clinical applications such as in dermatology.

In vivo near-realtime volumetric optical-resolution photoacoustic microscopy using a high-repetition-rate nanosecond fiber-laser

Optical-resolution photoacoustic microscopy (OR-PAM) is capable of achieving optical-absorption-contrast images with micron-scale spatial resolution. Previous OR-PAM systems have been frame-rate limited by mechanical scanning speeds and laser pulse repetition rate (PRR). We demonstrate OR-PAM imaging using a diode-pumped nanosecond-pulsed Ytterbium-doped 532-nm fiber laser with PRR up to 600 kHz. Combined with fast-scanning mirrors, our proposed system provides C-scan and 3D images with acquisition frame rate of 4 frames per second (fps) or higher, two orders of magnitude faster than previously published systems. High-contrast images of capillary-scale microvasculature in a live Swiss Webster mouse ear with ~6-µm optical lateral spatial resolution are demonstrated.

Glancing angle deposited nanostructured film Fabry-Perot etalons for optical detection of ultrasound

In this paper a new class of optical Fabry-Perot-based ultrasound detectors using low acoustic impedance glancing angle deposited (GLAD) films is demonstrated. GLAD is a single-step physical vapor-deposition (PVD) technique used to fabricate porous nanostructured thin films. Using titanium dioxide (TiO(2)), a transparent semiconductor with a high refractive index (n = 2.4), the GLAD technique can be employed to fabricate samples with tailored nano-porosity, refractive index periodicities, and high Q-factor reflectance spectra. The average acoustic impedance of the porous films is lower than bulk materials which will improve acoustic coupling, especially for high acoustic frequencies. For this work, two filters with high reflection in the C-band range and high transparency in the visible range (~80%) using GLAD films were fabricated. A 23 µm Parylene C layer was sandwiched between these two GLAD films in order to form a GLAD Fabry Perot Interferometer (GLAD-FPI). A high speed tunable continuous wavelength C-band laser was focused at the FPI and the reflection was measured using a high speed photodiode. The ultrasound pressure modulated the optical thickness of the FPI and hence its reflectivity. The fabricated sensor was tested using a 10 MHz unfocused transducer. The ultrasound transducer was calibrated using a hydrophone. The minimum detectable acoustic pressure was measured as 80 ± 20 Pa and the -3dB bandwidth was measured to be 18 MHz. This ultra-sensitive sensor can be an alternative to piezoelectric ultrasound transducers for any techniques in which ultrasound waves need to be detected including ultrasonic and photoacoustic imaging modalities. We demonstrate our GLAD-FPI for photoacoustic signal detection in optical-resolution photoacoustic microscopy (OR-PAM). To the best of our knowledge, this is the first time that a FPI fabricated using the GLAD method has been used for ultra-sensitive ultrasound detection.

In-Vivo functional optical-resolution photoacoustic microscopy with stimulated Raman scattering fiber-laser source.

In this paper a multi-wavelength optical-resolution photoacoustic microscopy (OR-PAM) system using stimulated Raman scattering is demonstrated for both phantom and in vivo imaging. A 1-ns pulse width ytterbium-doped fiber laser is coupled into a single-mode polarization maintaining fiber. Discrete Raman-shifted wavelength peaks extending to nearly 800 nm are generated with pulse energies sufficient for OR-PAM imaging. Bandpass filters are used to select imaging wavelengths. A dual-mirror galvanometer system was used to scan the focused outputs across samples of carbon fiber networks, 200μm dye-filled tubes, and Swiss Webster mouse ears. Photoacoustic signals were collected in transmission mode and used to create maximum amplitude projection C-scan images. Double dye experiments and in vivo oxygen saturation estimation confirmed functional imaging potential.

Label-free in vivo GRIN-lens optical resolution photoacoustic micro-endoscopy

In this letter, the feasibility of label-free in vivo GRIN-lens optical resolution photoacoustic micro-endoscopy is demonstrated. An image guide with 100 000 single-mode fibers in a 1.4 mm diameter bundle in conjunction with a 0.29 pitch GRIN lens is used in order to transfer a focused scanning spot through the image guide and refocus it into tissue. A high-repetition-rate (up to 600 kHz) ytterbium fiber laser is used in order to enable near real-time imaging capability. Phantom studies indicate 6 μm resolution. The system, with ~2 mm working distance, overcomes the penetration depth limitation and hence improves the surface laser fluence of previously reported fiber based optical resolution photoacoustic microscopy (OR-PAM). The proposed system with a sub-mm probe footprint is very flexible and now has a significant penetration depth which is another step towards clinical applications.

WIDE-BAND HYBRID AMPLIFIER OPERATING IN S-BAND REGION

Wide-band hybrid amplifier is theoretically proposed using a series configuration of Thulium-doped fiber amplifier (TDFA) and fiber Raman amplifier (FRA), which using the similar type of pump laser. The operating wavelength of this amplifier covers the bandwidth of entire short wavelength band (S-band) region by combining the gain spectrum of TDFA and FRA. The theoretical gain varies from 20 to 24dB within a wavelength region from 1460 to 1525nm and which is in a good agreement with the experimental result. The development of reliable high-power diode lasers in the 1420nm wavelength range will make this type of wide-band hybrid amplifier an interesting candidate for S-band optical telecommunication systems.

Multifocus optical-resolution photoacoustic microscopy using stimulated Raman scattering and chromatic aberration

In this Letter, multifocus optical-resolution photoacoustic microscopy is demonstrated using wavelength tuning and chromatic aberration for depth scanning. Discrete focal zones at several depth locations were created by refocusing light from a polarization-maintaining single-mode fiber pumped by a nanosecond fiber laser. The fiber and laser parameters were chosen to take advantage of stimulated Raman scattering (SRS) in the fiber to create a multiwavelength output that could then be bandpass filtered. The collimator lens and objective lens are chosen to take advantage of chromatic aberration in which each generated SRS wavelength peak focuses at a slightly different depth. The maximum amplitude of photoacoustic signals is mapped to form C-scan images. Additionally, all wavelength peaks fired simultaneously offers improved depth-of-field structural imaging at the cost of slight degradation of mainlobe-to-sidelobe ratios. Wavelength-tuned depth scanning over more than 440 μm is demonstrated, significantly greater than the ~100 μm depth of field predicted from our focused Gaussian beams. The improved depth of focus could be valuable for structural imaging of microvascular morphology without the need for mechanical scanning in the depth direction.

Integrated micro-endoscopy system for simultaneous fluorescence and optical-resolution photoacoustic imaging.

We present a new integrated micro-endoscopy system combining label-free, fiber-based, real-time C-scan optical-resolution photoacoustic microscopy (F-OR-PAM) and a high-resolution fluorescence micro-endoscopy system for visualizing fluorescently labeled cellular components and optically absorbing microvasculature simultaneously. With a diode-pumped 532-nm fiber laser, the F-OR-PAM sub-system is able to reach a resolution of ∼7  μm. The fluorescence subsystem, which does not require any mechanical scanning, consists of a 447.5-nm-centered diode laser as the light source, an objective lens, and a CCD camera. Proflavine is used as the fluorescent contrast agent by topical application. The scanning laser and the diode laser light source share the same light path within an optical fiber bundle containing 30,000 individual single-mode fibers. The absorption of proflavine at 532 nm is low, which mitigates absorption bleaching of the contrast agent by the photoacoustic excitation source. We demonstrate imaging in live murine models. The system is able to provide cellular morphology with cellular resolution co-registered with the structural information given by F-OR-PAM. Therefore, the system has the potential to serve as a virtual biopsy technique, helping visualize angiogenesis and the effects of anti-cancer drugs on both cells and the microcirculation, as well as aid in the study of other diseases.

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.