[Show abstract][Hide abstract] ABSTRACT: We present a microscope paradigm that performs differential interference
imaging with high sensitivity via optical amplification and radio-frequency
(RF) heterodyne detection. This method, termed differentially-enhanced sideband
imaging via radio-frequency encoding (DESIRE), uniquely exploits
frequency-to-space mapping technique to encode the image of an object onto the
RF sidebands of an illumination beam. As a proof-of-concept, we show validation
experiment by implementing radio frequency (f = 15 GHz) phase modulation in
conjunction with spectrally-encoded laser scanning technique to acquire
one-dimensional image of a barcode-like object using a commercial RF spectrum
[Show abstract][Hide abstract] ABSTRACT: Intravascular optical coherence tomography (IVOCT) is a well-established method for the high-resolution investigation of atherosclerosis in vivo. Intravascular near-infrared fluorescence (NIRF) imaging is a novel technique for the assessment of molecular processes associated with coronary artery disease. Integration of NIRF and IVOCT technology in a single catheter provides the capability to simultaneously obtain co-localized anatomical and molecular information from the artery wall. Since NIRF signal intensity attenuates as a function of imaging catheter distance to the vessel wall, the generation of quantitative NIRF data requires an accurate measurement of the vessel wall in IVOCT images. Given that dual modality, intravascular OCT-NIRF systems acquire data at a very high frame-rate (>100 frames/s), a high number of images per pullback need to be analyzed, making manual processing of OCT-NIRF data extremely time consuming. To overcome this limitation, we developed an algorithm for the automatic distance-correction of dual-modality OCT-NIRF images. We validated this method by comparing automatic to manual segmentation results in 180 in vivo images from six New Zealand White rabbit atherosclerotic after indocyanine-green injection. A high Dice similarity coefficient was found (0.97 ± 0.03) together with an average individual A-line error of 22 µm (i.e., approximately twice the axial resolution of IVOCT) and a processing time of 44 ms per image. In a similar manner, the algorithm was validated using 120 IVOCT clinical images from eight different in vivo pullbacks in human coronary arteries. The results suggest that the proposed algorithm enables fully automatic visualization of dual modality OCT-NIRF pullbacks, and provides an accurate and efficient calibration of NIRF data for quantification of the molecular agent in the atherosclerotic vessel wall.
The International Journal of Cardiovascular Imaging 10/2014; DOI:10.1007/s10554-014-0556-z · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Owing to its superior resolution, intravascular optical coherence tomography (IVOCT) is a promising tool for imaging the microstructure of coronary artery walls. However, IVOCT does not identify chemicals and molecules in the tissue, which is required for a more complete understanding and accurate diagnosis of coronary disease. Here we present a dual-modality imaging system and catheter that uniquely combines IVOCT with diffuse near-infrared spectroscopy (NIRS) in a single dual-modality imaging device for simultaneous acquisition of microstructural and compositional information. As a proof-of-concept demonstration, the device has been used to visualize co-incident microstructural and spectroscopic information obtained from a diseased cadaver human coronary artery.
[Show abstract][Hide abstract] ABSTRACT: Laser scanners are essential for scientific research, manufacturing, defense, and medical practice. Unfortunately, often times the speed of conventional laser scanners (e.g., galvanometric mirrors and acousto-optic deflectors) falls short for many applications, resulting in motion blur and failure to capture fast transient information. Here, we present a novel type of laser scanner that offers roughly three orders of magnitude higher scan rates than conventional methods. Our laser scanner, which we refer to as the hybrid dispersion laser scanner, performs inertia-free laser scanning by dispersing a train of broadband pulses both temporally and spatially. More specifically, each broadband pulse is temporally processed by time stretch dispersive Fourier transform and further dispersed into space by one or more diffractive elements such as prisms and gratings. As a proof-of-principle demonstration, we perform 1D line scans at a record high scan rate of 91 MHz and 2D raster scans and 3D volumetric scans at an unprecedented scan rate of 105 kHz. The method holds promise for a broad range of scientific, industrial, and biomedical applications. To show the utility of our method, we demonstrate imaging, nanometer-resolved surface vibrometry, and high-precision flow cytometry with real-time throughput that conventional laser scanners cannot offer due to their low scan rates.
Frontiers in Ultrafast Optics: Biomedical, Scientific, and Industrial Applications XIII conference, SPIE LASE; 03/2013
[Show abstract][Hide abstract] ABSTRACT: Real-time wideband digitizers are the key building block in many systems including oscilloscopes, signal intelligence, electronic warfare, and medical diagnostics systems. Continually extending the bandwidth of digitizers has hence become a central challenge in electronics. Fortunately, it has been shown that photonic pre-processing of wideband signals can boost the performance of electronic digitizers. In this article, the underlying principle of the time-stretch analog-to-digital converter (TSADC) that addresses the demands on resolution, bandwidth, and spectral efficiency is reviewed. In the TSADC, amplified dispersive Fourier transform is used to slow down the analog signal in time and hence to compress its bandwidth. Simultaneous signal amplification during the time-stretch process compensates for parasitic losses leading to high signal-to-noise ratio. This powerful concept transforms the analog signal's time scale such that it matches the slower time scale of the digitizer. A summary of time-stretch technology's extension to high-throughput single-shot spectroscopy, a technique that led to the discovery of optical rouge waves, is also presented. Moreover, its application in high-throughput imaging, which has recently led to identification of rogue cancer cells in blood with record sensitivity, is discussed.
[Show abstract][Hide abstract] ABSTRACT: We describe a real-time image processor that has enabled a new automated flow through microscope to screen cells in flow at 100,000 cells/s and a record false positive rate of one in a million. This unit is integrated with an ultrafast optical imaging modality known as serial time-encoded amplified microscopy (STEAM) for blur-free imaging of particles in high-speed flow. We show real-time image-based identification and screening of budding yeast cells and rare breast cancer cells in blood. The system generates E-slides (an electronic version of glass slides) on which particles of interest are digitally analyzed.
Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI conference, SPIE BiOS; 02/2013
[Show abstract][Hide abstract] ABSTRACT: We present a digital postprocessing linearization technique to efficiently suppress dynamic distortions added to a wideband signal in an analog optical link. Our technique achieves up to 35 dB suppression of intermodulation distortions over multiple octaves of signal bandwidth. In contrast to conventional linearization methods, it does not require excessive analog bandwidth for performing digital correction. This is made possible by regenerating undesired distortions from the captured output, and subtracting it from the distorted digitized signal. Moreover, we experimentally demonstrate a record spurious-free dynamic range of 120 dB·Hz<sup>2/3</sup> over a 6 GHz electrical signal bandwidth. While our digital broadband linearization technique advances state-of-the-art optical links, it can also be applied to other nonlinear dynamic systems.
[Show abstract][Hide abstract] ABSTRACT: We report high-throughput optical coherence tomography (OCT) that offers 1,000 times higher axial scan rate than conventional OCT in the 800 nm spectral range. This is made possible by employing photonic time-stretch for chirping a pulse train and transforming it into a passive swept source. We demonstrate a record high axial scan rate of 90.9 MHz. To show the utility of our method, we also demonstrate real-time observation of laser ablation dynamics. Our high-throughput OCT is expected to be useful for industrial applications where the speed of conventional OCT falls short.
[Show abstract][Hide abstract] ABSTRACT: We propose and demonstrate an all-optical time-stretch digitizer for real-time capture of ultrafast optical signals, beyond the bandwidths achievable by electronics. This approach uniquely combines four-wave mixing and photonic time-stretch technique to slow down and record high-speed optical signals. As a proof-of-concept, real-time recording of 40-Gb/s non-return-to-zero on-off-keying optical data stream is experimentally demonstrated using a stretch factor of 54 and 1.5-GHz back-end electronic bandwidth. We also report on the observation of dispersion penalty and its mitigation via single-sideband conversion enabled by an optical bandpass filter. Our technique may provide a path to real-time capture of ultrahigh-speed optical data streams.
[Show abstract][Hide abstract] ABSTRACT: Optical microscopy is one of the most widely used diagnostic methods in scientific, industrial, and biomedical applications. However, while useful for detailed examination of a small number (< 10,000) of microscopic entities, conventional optical microscopy is incapable of statistically relevant screening of large populations (> 100,000,000) with high precision due to its low throughput and limited digital memory size. We present an automated flow-through single-particle optical microscope that overcomes this limitation by performing sensitive blur-free image acquisition and nonstop real-time image-recording and classification of microparticles during high-speed flow. This is made possible by integrating ultrafast optical imaging technology, self-focusing microfluidic technology, optoelectronic communication technology, and information technology. To show the system's utility, we demonstrate high-throughput image-based screening of budding yeast and rare breast cancer cells in blood with an unprecedented throughput of 100,000 particles/s and a record false positive rate of one in a million.
Proceedings of the National Academy of Sciences 07/2012; 109(29):11630-5. DOI:10.1073/pnas.1204718109 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We propose an all-optical time-stretch oscilloscope, combining four-wave mixing and time-stretch technique for real-time capture of ultrafast optical time-series, beyond the bandwidths achievable by electronics. As a proof-of-concept, we demonstrate capture of 40-Gbits/s optical data.
[Show abstract][Hide abstract] ABSTRACT: Laser scanning technology is one of the most integral parts of today's scientific research, manufacturing, defense, and biomedicine. In many applications, high-speed scanning capability is essential for scanning a large area in a short time and multi-dimensional sensing of moving objects and dynamical processes with fine temporal resolution. Unfortunately, conventional laser scanners are often too slow, resulting in limited precision and utility. Here we present a new type of laser scanner that offers ∼1,000 times higher scan rates than conventional state-of-the-art scanners. This method employs spatial dispersion of temporally stretched broadband optical pulses onto the target, enabling inertia-free laser scans at unprecedented scan rates of nearly 100 MHz at 800 nm. To show our scanner's broad utility, we use it to demonstrate unique and previously difficult-to-achieve capabilities in imaging, surface vibrometry, and flow cytometry at a record 2D raster scan rate of more than 100 kHz with 27,000 resolvable points.
[Show abstract][Hide abstract] ABSTRACT: We present a digital post-processing linearization technique to suppress dynamic distortions added to a wideband signal in an analog optical link. We demonstrate record spurious-free dynamic range of 120 dB.Hz2/3 over 6-GHz electrical signal bandwidth.
[Show abstract][Hide abstract] ABSTRACT: High-speed high-contrast imaging modalities that enable image acquisition of transparent media without the need for chemical staining are essential tools for a broad range of applications; from semiconductor process monitoring to blood screening. Here we introduce a method for contrast-enhanced imaging of unstained transparent objects that is capable of high-throughput imaging. This method combines the Nomarski phase contrast capability with the ultrahigh frame rate and shutter speed of serial time-encoded amplified microscopy. As a proof of concept, we show imaging of a transparent test structure and white blood cells in flow at a shutter speed of 33 ps and a frame rate of 36.1 MHz using a single-pixel photo-detector. This method is expected to be a valuable tool for high-throughput screening of unstained cells.
[Show abstract][Hide abstract] ABSTRACT: Optical performance monitoring of high-capacity networks is one of the enabling technologies of future reconfigurable optical switch networks. In such networks, rapid performance evaluation of data streams becomes challenging due to the use of advanced modulation formats and high data rates. The time-stretch enhanced recording oscilloscope offers a potential solution to monitoring high-rate data in a practical time scale. Here we demonstrate an architecture with a differential detection front end for simultaneous I/Q data monitoring of a 100 gigabits/s return-to-zero differential quadrature phase-shift keying signal. This demonstration shows the potential of this technology for rapid performance monitoring of high-rate optical data streams that employ advanced modulation formats.
[Show abstract][Hide abstract] ABSTRACT: Dual-polarization photonic time-stretch technique, which exploits polarization multiplexing to improve the spectral efficiency of the conventional photonic time-stretch technique, is proposed. This technique reduces the demand on optical bandwidth for large record length of the photonic time-stretch analog-to-digital converter. It is shown that this technique can capture high-bandwidth radio-frequency signals (>;10-GHz instantaneous bandwidth). Experimentally, 12.5-Gb/s data eye-diagram measurement using this preprocessor operating in equivalent-time mode is demonstrated.
[Show abstract][Hide abstract] ABSTRACT: Wideband real-time analog-to-digital converters are the central tools in waveform analyzers, communication systems, and radar technology. Photonic time-stretch analog-to-digital converters (TSADCs) utilize a broadband optical source and an optical link to extend the capabilities of real-time digitizers, allowing acquisition of wideband radio frequency (RF) signals with high resolution. In the TSADC, it is desirable to improve the signal-to-noise-and-distortion ratio and effective number of bits by increasing the optical power. Here, we numerically evaluate the impact of optical nonlinearity on TSADC performance. It is demonstrated that the optical nonlinearity can impose an upper limit on the effective number of bits and that the RF bandwidth limitation due to dispersion penalty depends on optical power. The trends presented here can also be applied to other optical links in which optical nonlinearity and dispersion are significant.
[Show abstract][Hide abstract] ABSTRACT: We show how the ability to slow down, amplify, and capture fast transient
events can produce high-throughput real-time instruments ranging from
digitizers to imaging flow cytometers for detection of rare diseased cells in
[Show abstract][Hide abstract] ABSTRACT: We report simultaneous I/Q-data monitoring of 100-Gb/s RZ-DQPSK signal using a two-channel time-stretch enhanced recording (TiSER) oscilloscope. TiSER offers a solution to monitoring of high bit rate data.
[Show abstract][Hide abstract] ABSTRACT: We report a new method of high-contrast imaging of unstained and transparent objects at ~1000 times higher frame rates than conventional methods. As a proof-of-concept, we demonstrate enhanced image-contrast in 2D imaging of a transmission grating.