Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity

We have developed a novel phase-resolved optical coherence tomography (OCT) and optical Doppler tomography (ODT) system that uses phase information derived from a Hilbert transformation to image blood flow in human skin with fast scanning speed and high velocity sensitivity. Using the phase change between sequential scans to construct flow-velocity imaging, this technique decouples spatial resolution and velocity sensitivity in flow images and increases imaging speed by more than 2 orders of magnitude without compromising spatial resolution or velocity sensitivity. The minimum flow velocity that can be detected with an axial-line scanning speed of 400 Hz and an average phase change over eight sequential scans is as low as 10 microm/s, while a spatial resolution of 10 microm is maintained. Using this technique, we present what are to our knowledge the first phase-resolved OCT/ODT images of blood flow in human skin.     

Doppler standard deviation imaging for clinical monitoring of in vivo human skin blood flow

We used a novel phase-resolved optical Doppler tomographic (ODT) technique with very high flow-velocity sensitivity (10microm/s) and high spatial resolution (10microm) to image blood flow in port-wine stain (PWS) birthmarks in human skin. In addition to the regular ODT velocity and structural images, we use the variance of blood flow velocity to map the PWS vessels. Our device combines ODT and therapeutic systems such that PWS blood flow can be monitored in situ before and after laser treatment. To the authors' knowledge this is the first clinical application of ODT to provide a fast semiquantitative evaluation of the efficacy of PWS laser therapy in situ and in real time.     

3D MR microscopy with resolution 3.7 microm by 3.3 microm by 3.3 microm

The technique of magnetic resonance imaging microscopy holds promise of bringing the full capabilities of NMR to arbitrarily specified positions within spatially inhomogeneous systems, including biological cells, yet the possibilities are limited by the need for adequate sensitivity and spatial resolution. We report proton magnetic resonance images obtained by combining advances in receiver coil sensitivity, gradient strength, and pulse/gradient sequence design. We achieve resolution of 3.7 +/- 0.4 microm by 3.3 +/- 0.3 microm by 3.3 +/- 0.3 microm for a volume resolution approximately 40 femtoliters (corresponding to approximately 3 x 10(12) proton spins).     

Three-dimensional tracking of fluorescent nanoparticles with subnanometer precision by use of off-focus imaging

We show that the position of a fluorescent nanoparticle can be measured in three dimensions with subnanometer precision and 100-ms temporal resolution by use of standard epifluorescence video imaging in off-focus mode. The particle can be tracked without feedback in a volume of at least 40 microm x 60 microm x 3 microm. With the technique presented, the structure-mobility relationship of 216-nm latex particle in a porous polymer network was studied in three dimensions.     

Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography

We report the development of an optical technique for noninvasive imaging of in vivo blood flow dynamics and tissue structures with high spatial resolution (2-10 microm) in biological systems. The technique is based on optical Doppler tomography (ODT), which combines Doppler velocimetry with optical coherence tomography to measure blood flow velocity at discrete spatial locations. The exceptionally high resolution of ODT permits noninvasive in vivo imaging of both blood microcirculation and tissue structures surrounding the vessel, which has significance for biomedical research and clinical applications. Tomographic imaging of in vivo blood flow velocity in the chick chorioallantoic membrane and in rodent skin is demonstrated.     

Slanted hole array beam profiler (SHArP)-a high-resolution portable beam profiler based on a linear aperture array

We demonstrate a novel high-resolution portable beam profiler based on a slanted linear array of small apertures, termed a slanted hole array beam profiler (SHArP). The apertures are directly fabricated on a metal-coated CMOS imaging sensor. With a single linear scan, the aperture array can establish a virtual grid of sampling points for beam profiling. With our prototype, we demonstrate beam profiling of Gaussian beams over an area of 66.5 microm x 66.5 microm with a resolution of 0.8 microm (compare with the CMOS pixel size of 10 microm). The resolution can be improved into the range of submicrometers by fabricating smaller apertures. The good correspondence between the measured and calculated beam profiles proves the fidelity of our new beam profiling scheme.     

Spatial and temporal resolution effects on dynamic contrast-enhanced magnetic resonance mammography

We tested the hypothesis that partial volume effects due to poor in-plane resolution and/or low temporal resolution used in clinical dynamic contrast-enhanced magnetic resonance imaging results in erroneous diagnostic information based on inaccurate estimates of tumor contrast agent extravasation and tested whether reduced encoding techniques can correct for dynamic data volume averaging. Image spatial resolution was reduced from 469 x 469 microm2 to those reported below by selecting a subset of k-space data. We then compared the top five K(trans)/V(T) "hot spots" obtained from the original data set, 469 x 469-microm in-plane spatial resolution and an 18-s temporal resolution processed by fast Fourier transform (FFT), with values obtained from data sets having in-plane spatial resolutions of 938 x 938, 1875 x 1875 and 2500 x 2500 microm2 and a temporal resolution of 18 s, or data sets with temporal resolutions of 36, 54 and 72 and a spatial resolution of 469 x 469 microm2, and found them to statistically differ from the parent data sets. We then tested four different post processing methods for improving the spatial resolution without sacrificing temporal resolution: zero-filled FFT, keyhole, reduced-encoding imaging by generalized-series reconstruction (RIGR) and two-reference RIGR (TRIGR). The top five values of K(trans)/V(T) obtained from data sets, the in-plane spatial resolutions of which were improved to 469 x 469 microm2 by zero-filling FFT, Keyhole and RIGR, statistically differed from those obtained from the original 469 x 469 microm2 FFT parent image data set. Only the 938 x 938 and 1875 x 1875 microm2 data sets reconstructed to 469 x 469 microm2 with TRIGR reconstruction method yielded values of the top five K(trans)/V(T) hot spots statistically the same as the original parent data set, 469 x 469 microm2 in-plane spatial and 18-s temporal-resolution FFT. That is, partial volume effects from data sets of different in-plane spatial resolution resulted in statistically different values of the top five K(trans)/V(T) hot spots relative to a high spatial and temporal resolution data set, and TRIGR reconstruction of these low resolution data sets to high resolution images provided statistically similar values with a savings in temporal resolution of 2 to 4 times.     

Fiber-optic-bundle-based optical coherence tomography

A fiber-optic-bundle-based optical coherence tomography (OCT) probe method is presented. The experimental results demonstrate this multimode optical fiber-bundle-based OCT system can achieve a lateral resolution of 12 microm and an axial resolution of 10 microm with a superluminescent diode source. This novel OCT imaging approach eliminates any moving parts in the probe and has a primary advantage for use in extremely compact and safe OCT endoscopes for imaging internal organs and great potential to be combined with confocal endoscopic microscopy.     

Extended focus depth for Fourier domain optical coherence microscopy

We report on a new detection scheme for Fourier domain optical coherence microscopy that exhibits high transverse resolution along an axially extended focal range. Nearly constant transverse resolution of approximately 1.5 microm along a focal range of 200 microm is experimentally verified with a maximum sensitivity of 105 dB. A broad-bandwidth Ti:sapphire laser allowed for an axial resolution of 3 microm in air.     

One micrometer resolution NMR microscopy

We obtained a magnetic resonance image of 1 microm resolution and 75 microm(3) voxel volume for a phantom filled with hydrocarbon oil within an hour at 14.1 T. For this work, a specially designed probe with a high sensitivity RF coil and gradient coils generating over 1000 G/cm was built. The optimal pulse sequence was analyzed in consideration of the bandwidth, diffusion coefficients, and T(1) and T(2) relaxations of the medium. The system was applied to the in vivo imaging of a geranium leaf stem to get the images of 2 microm resolution and 200 microm(3) voxel volume.     

Three dimensional magnetic resonance imaging by magnetic resonance force microscopy with a sharp magnetic needle

An electropolished magnetic needle made of Nd(2)Fe(14)B permanent magnet was used for obtaining better spatial resolution than that achieved in our previous work. We observed the magnetic field gradient |G(Z)|=80.0G/microm and the field strength B=1250G at Z approximately 8.8 microm from the top of the needle. The use of this needle for three dimensional magnetic resonance force microscopy at room temperature allowed us to achieve the voxel resolution to be 0.6 microm x 0.6 microm x 0.7 microm in the reconstructed image of DPPH phantom. The acquisition time spent for the whole data collection over 64 x 64 x 16 points, including an iterative signal average by six times per point, was about 10 days.     

Confocal reflectance theta line scanning microscope for imaging human skin in vivo

A confocal reflectance theta line scanning microscope demonstrates imaging of nuclear and cellular detail in human epidermis in vivo. Experimentally measured line-spread functions determine the instrumental optical section thickness to be 1.7 +/- 0.1 microm and the lateral resolution to be 1.0 +/- 0.1 microm. Within human dermis (through full-thickness epidermis), the measured section thickness is 9.2 +/- 1.7 microm and the lateral resolution is 1.7 +/- 0.1 microm. An illumination line is scanned directly in the pupil of the objective lens, and the backscattered descanned light is detected with a linear array, such that the theta line scanner consists of only seven optical components.     

X-ray resonance in crystal cavities: realization of Fabry-Perot resonator for hard x rays

X-ray back diffraction from monolithic two silicon crystal plates of 25-150 microm thickness and a 40-150 microm gap using synchrotron radiation of energy resolution DeltaE = 0.36 meV at 14.4388 keV clearly show resonance fringes inside the energy gap and the total-reflection range for the (12 4 0) reflection. This cavity resonance results from the coherent interaction between the x-ray wave fields generated by the two plates with a gap smaller than the x-ray coherence length. This finding opens up new opportunities for high-resolution and phase-contrast x-ray studies, and may lead to new developments in x-ray optics.     

Use of two-photon absorption in a photorefractive crystal for three-dimensional optical memory

We describe the use of two-photon absorption in a photorefractive crystal for recording bit data in multilayered optical memory. A short-pulse near-infrared laser is used for generating the photorefractive effect by two-photon absorption. We succeeded in recording and reading seven layers of data in a LiNbO(3) crystal with a lateral resolution (distance between bits) of 5microm and an axial resolution (distance between layers) of 20 microm .     

Dual-wedge scanning confocal reflectance microscope

A confocal reflectance microscope has been developed that incorporates a dual-wedge scanner to reduce the size of the device relative to current raster scanning instruments. The scanner is implemented with two prisms that are rotated about the optical axis. Spiral and rosette scans are performed by rotating the prisms in the same or opposite directions, respectively. Experimental measurements show an on-axis lateral resolution of 1.6 microm and optical sectioning of 4.7 microm, which compares with a diffraction-limited resolution of 0.8 and 1.9 microm, respectively.     

Local waiting time fluctuations along a randomly pinned crack front

The propagation of an interfacial crack along a heterogeneous weak plane of a transparent Plexiglas block is followed using a high resolution fast camera. We show that the fracture front dynamics is governed by local and irregular avalanches with very large size and velocity fluctuations. We characterize the intermittent dynamics observed, i.e., the local pinnings and depinnings of the crack front by measuring the local waiting time fluctuations along the crack front during its propagation. The deduced local front line velocity distribution exhibits a power law behavior, P(v) alpha v-eta with eta=2.55+/-0.15, for velocities v larger than the average front speed . The burst size distribution is also a power law, P(S) alpha S-gamma with gamma=1.7+/-0.1. Above a characteristic length scale of disorder Ld approximately 15 microm, the avalanche clusters become anisotropic providing an estimate of the roughness exponent of the crack front line, H=0.66.     

Wavelength-dispersive device based on a Fourier-transform Michelson-type arrayed waveguide grating

We propose a new type of arrayed waveguide grating (AWG) device that operates as a Fourier-transform (FT) spectrometer without the need of scanning elements. The large input aperture size typical of a FT spectrometer eliminates the requirement for a narrow single-mode input waveguide while still achieving high spectral resolution with a markedly increased light-gathering capability (etendue). An example of the device with a resolution of 0.07 nm (approximately 10 GHz) and designed for a silicon-on-insulator platform is presented. The calculated spectra show no noticeable deterioration for aperture widths as large as 40 microm, yielding more than a 50-fold increase in aperture size compared with conventional AWG or echelle grating based devices at the equivalent resolution.     

Rapid imaging of fluid flow patterns in a narrow packed bed using MRI

A gradient echo rapid velocity and acceleration imaging sequence (GERVAIS) has been developed and implemented to image liquid flow within a narrow packed bed. Two-dimensional velocity images have been acquired with an in-plane pixel size of 781 microm x 781 microm, with a data acquisition time of 20 ms for a single velocity component. Images of the x, y and z velocity vectors are reported. Data are reported for Reynolds numbers (based on particle diameter) of 200 and 300. In each case, GERVAIS images are compared with the results of a standard spin-echo phase-encoding velocity measurement. At Re = 200, steady-state flow is expected and the velocity images acquired using both techniques are consistent. At Re = 300, the GERVAIS sequence is able to image the unsteady-state flow field within this system. In contrast, the standard phase-encoding velocity measurement contains significant artefacts.     

Simultaneous measurements of three-dimensional reflectivity distributions in scattering media based on optical frequency-domain reflectometry

A new type of tomography system based on optical frequency-domain reflectometry is presented. Using an area sensor, the system can simultaneously measure three-dimensional reflectivity distributions in scattering media without the need for mechanical scanning. In preliminary experiments we demonstrate that a target (resolution chart) placed behind biological tissue can be imaged with high depth resolution (47 microm) for a short measurement time.     

Extended continuous-wave supercontinuum generation in a low-water-loss holey fiber

We report on the development of a 2.5 microm core photonic crystal fiber with a substantially reduced water-peak loss around 1.38 microm, which allows extended Raman-soliton supercontinuum generation up to 1.55 microm with a cw ytterbium fiber laser pump source. The resulting broadband, high-spectral-power-density, low-coherence light source can be employed for advanced, submicrometer resolution optical coherence tomography.