We report an imaging method, termed Fourier ptychographic microscopy (FPM), which iteratively stitches together a
number of variably illuminated, low-resolution intensity images in Fourier space to produce a wide-field, high-resolution
complex sample image. By adopting a wavefront correction strategy, the FPM method can also correct for aberrations and
digitally extend a microscope’s depth of focus beyond the physical limitations of its optics. As a demonstration, we built a
microscope prototype with a resolution of 0.78 µm, a field of view of ∼120 mm^2 and a resolution-invariant depth of focus
of 0.3 mm (characterized at 632 nm). Gigapixel colour images of histology slides verify successful FPM operation. The
reported imaging procedure transforms the general challenge of high-throughput, high-resolution microscopy from one
that is coupled to the physical limitations of the system’s optics to one that is solvable through computation.

Wide-field, high-resolution Fourier ptychographic microscopy

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

The diffraction tomography theorem is adapted to one-dimensional length measurement. The resulting spectral interferometry technique is described and the first length measurements using this technique on a model eye and on a human eye in vivo are presented.

Measurement of intraocular distances by backscattering spectral interferometry

In vivo imaging, which enables us to peer deeply within living subjects, is producing tremendous opportunities both for clinical diagnostics and as a research tool. Contrast material is often required to clearly visualize the functional architecture of physiological structures. Recent advances in nanomaterials are becoming pivotal to generate the high-resolution, high-contrast images needed for accurate, precision diagnostics. Nanomaterials are playing major roles in imaging by delivering large imaging payloads, yielding improved sensitivity, multiplexing capacity, and modularity of design. Indeed, for several imaging modalities, nanomaterials are now not simply ancillary contrast entities, but are instead the original and sole source of image signal that make possible the modality’s existence. We address the physicochemical makeup/design of nanomaterials through the lens of the physical properties that produce contrast signal for the cognate imaging modality—we stratify nanomaterials on the basis of thei...

Nanomaterials for In Vivo Imaging

We present a polarization-sensitive optical coherence-domain reflectometer capable of characterizing the phase retardation between orthogonal linear polarization modes at each reflection point in a birefringent sample. The device is insensitive to the rotation of the sample in the plane perpendicular to ranging. Phase measurement accuracy is ±0.86°, but the reflectometer can distinguish local variations in birefringence as small as 0.05° with a distance resolution of 10.8 μm and a dynamic range of 90 dB. Birefringence-sensitive ranging in a wave plate, an electro-optic modulator, and a calf coronary artery is demonstrated.

Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging

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.

/pdf/optical-coherence-tomography-today-speed-contrast-and-49xipxv43a.pdf

Optical coherence tomography today: speed, contrast, and multimodality.

A 218 mega-pixel synthetic aperture was collected by raster scanning a CCD detector in a digital holography imaging experiment. Frames were mosaicked together using a two-step cross-correlation registration. Phase correction using sharpness metrics were utilized to achieve diffraction-limited resolution.

High-resolution synthetic-aperture digital holography with digital phase and pupil correction.

This paper proposes a sub-aperture correlation based numerical phase correction method for interferometric full field imaging systems provided the complex object field information can be extracted. This method corrects for the wavefront aberration at the pupil/ Fourier transform plane without the need of any adaptive optics, spatial light modulators (SLM) and additional cameras. We show that this method does not require the knowledge of any system parameters. In the simulation study, we consider a full field swept source OCT (FF SSOCT) system to show the working principle of the algorithm. Experimental results are presented for a technical and biological sample to demonstrate the proof of the principle.

Subaperture correlation based digital adaptive optics for full field optical coherence tomography

High-resolution imaging of the human retina has always been a challenge due to imperfect optical properties of the human cornea and lens, which limit the achievable resolution. We present a noniterative digital aberration correction (DAC) to achieve aberration-free cellular-level resolution in optical coherence tomography (OCT) images of the human retina in vivo. The system used is a line-field spectral-domain OCT system with a high tomogram rate, reaching 2.5 kHz. Such a high speed enables us to successfully apply digital aberration correction for not only imaging of human cone photoreceptors but also to obtain an aberration- and defocus-corrected 3D volume. Additionally, we apply DAC on functional OCT angiography data to improve lateral resolution and compensate for defocus. The speed necessities for the use of DAC in patient imaging are quantified by measuring the axial motion of 36 subjects. The first demonstration of DAC on OCT angiography as well as the motion analysis is important for future work dealing with DAC.

Noniterative digital aberration correction for cellular resolution retinal optical coherence tomography in vivo

The purpose of this work is to investigate the benefits of adaptive optics (AO) technology for optical coherence tomography angiography (OCTA). OCTA has shown great potential in non-invasively enhancing the contrast of vessels and small capillaries. Especially the capability of the technique to visualize capillaries with a lateral extension that is below the transverse resolution of the system opens unique opportunities in diagnosing retinal vascular diseases. However, there are some limitations of this technology such as shadowing and projection artifacts caused by overlying vasculature or the inability to determine the true extension of a vessel. Thus, the evaluation of the vascular structure and density based on OCTA alone can be misleading. In this paper we compare the performance of AO-OCT, AO-OCTA and OCTA for imaging retinal vasculature. The improved transverse resolution and the reduced depth of focus of AO-OCT and AO-OCTA greatly reduce shadowing artifacts allowing for a better differentiation and segmentation of different vasculature layers of the inner retina. The comparison is done on images recorded in healthy volunteers and in diabetic patients with distinct pathologies of the retinal microvasculature.

Abhishek Kumar

Papers

Optical coherence tomography today: speed, contrast, and multimodality.

High-resolution synthetic-aperture digital holography with digital phase and pupil correction.

Subaperture correlation based digital adaptive optics for full field optical coherence tomography

Noniterative digital aberration correction for cellular resolution retinal optical coherence tomography in vivo

Visualization of micro-capillaries using optical coherence tomography angiography with and without adaptive optics.