Mengyang Liu

Optical coherence tomography today: speed, contrast, and multimodality

Abstract. In the last 25 years, optical coherence tomography (OCT) has advanced to be one of the most innovative and most successful translational optical imaging techniques, achieving substantial economic impact as well as clinical acceptance. This is largely owing to the resolution improvements by a factor of 10 to the submicron regime and to the imaging speed increase by more than half a million times to more than 5 million A-scans per second, with the latter one accomplished by the state-of-the-art swept source laser technologies that are reviewed in this article. In addition, parallelization of OCT detection, such as line-field and full-field OCT, has shortened the acquisition time even further by establishing quasi-akinetic scanning. Besides the technical improvements, several functional and contrast-enhancing OCT applications have been investigated, among which the label-free angiography shows great potential for future studies. Finally, various multimodal imaging modalities with OCT incorporated are reviewed, in that these multimodal implementations can synergistically compensate for the fundamental limitations of OCT when it is used alone.

Spectroscopic photoacoustic microscopy using a photonic crystal fiber supercontinuum source.

Photoacoustic microscopy (PAM) provides high resolution images with excellent image contrast based on optical absorption. The compact size and high repetition rate of pulsed microchip lasers make them attractive sources for PAM. However, their fixed wavelength output precludes their use in spectroscopic PAM. We are developing a tunable optical source based on a microchip laser that is suitable for spectroscopic PAM. Pulses from a 6.6 kHz repetition rate Q-switched Nd:YAG microchip laser are sent through a photonic crystal fiber with a zero dispersion wavelength at 1040 nm. The highly nonlinear optical propagation produces a supercontinuum spectrum spanning 500-1300 nm. A tunable band pass filter selects the desired wavelength band from the supercontinuum. Our PAM system employs optical focusing and a 25 MHz spherically focused detection transducer. En-face imaging experiments were performed at seven different wavelengths from 575 to 875 nm. A simple discriminant analysis of the multiwavelength photoacoustic data produces images that clearly distinguish the different absorbing regions of ink phantoms. These results suggest the potential of this compact tunable source for spectroscopic photoacoustic microscopy.

In vivo three dimensional dual wavelength photoacoustic tomography imaging of the far red fluorescent protein E2-Crimson expressed in adult zebrafish

For the first time the far red fluorescent protein (FP) E2-Crimson genetically expressed in the exocrine pancreas of adult zebrafish has been non-invasively mapped in 3D in vivo using photoacoustic tomography (PAT). The distribution of E2-Crimson in the exocrine pancreas acquired by PAT was confirmed using epifluorescence imaging and histology, with optical coherence tomography (OCT) providing complementary structural information. This work demonstrates the depth advantage of PAT to resolve FP in an animal model and establishes the value of E2-Crimson for PAT studies of transgenic models, laying the foundation for future longitudinal studies of the zebrafish as a model of diseases affecting inner organs.

Biometric Mapping of Fingertip Eccrine Glands With Optical Coherence Tomography

Biometric access control systems often employ fingerprint recognition based on the analysis of ridge patterns and minutiae. The inclusion of finer details, such as sweat pores, increases the accuracy of fingerprint identification. However, the distribution of sweat pores is difficult to extract from conventional fingerprint images, where image quality is susceptible to variations in fingertip surface conditions. Furthermore, a fingertip surface can be routinely counterfeited with a variety of techniques. We propose a more reliable biometric technology using spectral domain optical coherence tomography (SD-OCT) to image the subsurface of a fingertip. Experiments demonstrate high repeatability in clearly visualizing the distribution of sweat (eccrine) glands in live fingertips. Experiments on artificial fingertips confirm this is a spoof-proof approach. We believe these encouraging results demonstrate the value of SD-OCT as a robust fingerprint identification technology for biometric recognition.

In vivo dual-modality photoacoustic and optical coherence tomography imaging of human dermatological pathologies

Vascular abnormalities serve as a key indicator for many skin diseases. Currently available methods in dermatology such as histopathology and dermatoscopy analyze underlying vasculature in human skin but are either invasive, time-consuming, and laborious or incapable of providing 3D images. In this work, we applied for the first time dual-modality photoacoustic and optical coherence tomography that provides complementary information about tissue morphology and vasculature of patients with different types of dermatitis. Its noninvasiveness and relatively short imaging time and the wide range of diseases that it can detect prove the merits of the dual-modality imaging system and show the great potential of its clinical use in the future.

Dual modality optical coherence and whole-body photoacoustic tomography imaging of chick embryos in multiple development stages

Chick embryos are an important animal model for biomedical studies. The visualization of chick embryos, however, is limited mostly to postmortem sectional imaging methods. In this work, we present a dual modality optical imaging system that combines swept-source optical coherence tomography and whole-body photoacoustic tomography, and apply it to image chick embryos at three different development stages. The explanted chick embryos were imaged in toto with complementary contrast from both optical scattering and optical absorption. The results serve as a prelude to the use of the dual modality system in longitudinal whole-body monitoring of chick embryos in ovo.

Phase-stable swept source OCT angiography in human skin using an akinetic source

We demonstrate noninvasive structural and microvascular contrast imaging of human skin in vivo, using phase difference swept source OCT angiography (pOCTA). The pOCTA system employs an akinetic, all-semiconductor, highly phase-stable swept laser source which operates at 1340 nm central wavelength, with 37 nm bandwidth (at 0 dB region) and 200 kHz A-scan rate. The phase sensitive detection does not need any external phase stabilizing implementations, due to the outstanding high phase linearity and sweep phase repeatability within 2 mrad. We compare the performance of phase based OCTA to speckle based OCTA for visualizing human vascular networks. pOCTA shows better contrast especially for deeper vascular details as compared to speckle based OCTA. The phase stability of the akinetic source allows the OCTA system to show decent vascular contrast only with 2 B-scans. We compare the performance of using 2 versus 4 B-scans for calculating the vascular contrast. Finally, the performance of a 100 nm bandwidth akinetic laser at 1310 nm is investigated for both OCT and OCTA.

Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging

Cutaneous blood flow accounts for approximately 5% of cardiac output in human and plays a key role in a number of a physiological and pathological processes. We show for the first time a multi-modal photoacoustic tomography (PAT), optical coherence tomography (OCT) and OCT angiography system with an articulated probe to extract human cutaneous vasculature in vivo in various skin regions. OCT angiography supplements the microvasculature which PAT alone is unable to provide. Co-registered volumes for vessel network is further embedded in the morphologic image provided by OCT. This multi-modal system is therefore demonstrated as a valuable tool for comprehensive non-invasive human skin vasculature and morphology imaging in vivo.

Photoacoustic microscopy with a pulsed multi-color source based on stimulated Raman scattering

Photoacoustic microscopy (PAM) provides excellent image contrast based on optical absorption. A very common pulsed optical source is a frequency-doubled Q-switched Nd:YAG laser. However, the fixed 532 nm output is not suitable for spectroscopic PAM. We demonstrate a simple approach to increase the number of wavelengths by using stimulated Raman scattering (SRS) in an optical fiber. A sufficiently intense laser pulse nonlinearly interacts with the internal vibrations of the glass molecular structure to produce a series of down-shifted frequency components (Stokes lines). The number of spectral peaks depends on the fiber length, peak intensity, and polarization of the propagating laser pulse. We use a Q-switched Nd:YAG microchip laser producing 0.6 ns duration pulses at 1064 nm with 10 μJ of energy at a 7.5 kHz repetition rate. A 10 mm long frequency-doubling KTP crystal produces 2 μJ pulses at 532 nm. After passing through a half-wave plate for polarization control, the 532 nm laser pulses are coupled into a 6 meter long polarization-maintaining single-mode silica fiber. The multi-color fiber output goes through a band pass filter, where the selected wavelength is sent to a photoacoustic microscopy system employing optical focusing. The individual pulse energy is over 80 nJ at four wavelengths. Imaging experiments on scattering phantoms clearly distinguish tubes filled with red and blue inks. A major advantage of our technique is the simple arrangement to convert a single-wavelength laser into a multi-color source for spectroscopic PAM. The discrete number of Stokes lines does not allow arbitrary wavelength selection, but the wavelength spacing is sufficiently close for practical applications (e.g. oxygenation measurements). Straightforward improvements to the system can achieve pulse energies over 100 nJ, which is sufficient for in vivo applications. We believe this multi-color technique can significantly benefit spectroscopic photoacoustic microscopy.

All-optical highly sensitive akinetic sensor for ultrasound detection and photoacoustic imaging

A novel all-optical akinetic ultrasound sensor, consisting of a rigid, fiber-coupled Fabry-Pérot etalon with a transparent central opening is presented. The sensing principle relies exclusively on the detection of pressure-induced changes of the refractive index in the fluid filling the Fabry-Pérot cavity. This enables resonance-free, inherently linear signal detection over a broad bandwidth. We demonstrate that the sensor achieves a exceptionally low peak noise equivalent pressure (NEP) values of 2 Pa over a 20 MHz measurement bandwidth (without signal averaging), while maintaining a flat frequency response, and a detection bandwidth up to 22.5 MHz (-6 dB). The measured large full field of view of the sensor is 2.7 mm × 1.3 mm and the dynamic range is [Formula: see text] or 63 dB at 20 MHz bandwidth. For different required amplitude ranges the upper amplitude detection limit can be customized from at least 2 kPa to 2 MPa by using cavity mirrors with a lower optical reflectivity. Imaging tests on a resolution target and on biological tissue show the excellent suitability of the akinetic sensor for optical resolution photoacoustic microscopy (OR-PAM) applications.