Third Cumulant of the total Transmission of diffuse Waves

The probability distribution of the total transmission is studied for waves multiple scattered from a random, static configuration of scatterers. A theoretical study of the second and third cumulant of this distribution is presented. Within a diagrammatic approach a theory is developed which relates the third cumulant normalized to the average, $\langle \langle T_a^3 \rangle \rangle$, to the normalized second cumulant $\langle \langle T_a^2 \rangle \rangle$. For a broad Gaussian beam profile it is found that $\langle \langle T_a^3 \rangle \rangle= \frac{16}{5} \langle \langle T_a^2 \rangle \rangle^2$. This is in good agreement with data of optical experiments.Comment: 16 pages revtex, 8 separate postscript figure

Endo-microscopy beyond the Abbe and Nyquist limits

For several centuries, far-field optical microscopy has remained a key instrument in many scientific disciplines including physical, chemical and biomedical research. Nonetheless, far-field imaging has many limitations: the spatial resolution is controlled by the diffraction of light and the imaging speed follows Nyquist-Shannon sampling theorem. The recent development of super-resolution techniques has pushed the limits of spatial resolution. However, these methods typically require complicated setups, long acquisition time and are still not applicable for deep-tissue bioimaging. Here we report imaging through an ultra-thin fiber probe with a spatial resolution beyond the Abbe limit and a temporal resolution beyond the Nyquist limit simultaneously in a simple and compact setup. We use the random nature of mode coupling in a multimode fiber, the sparsity constraint and compressive sensing reconstruction. The new approach of super-resolution endo-microscopy does not use any specific properties of the fluorescent label such as depletion or stochastic activation of the molecular fluorescent state and therefore could be used for label-free imaging. We demonstrate a spatial resolution more than 2 times better than the diffraction limit and an imaging speed 20 times faster than the Nyquist limit. The proposed approach could significantly expand the realm of the application of nanoscopy for bioimaging.Comment: 22 pages, 6 figures, supplementary materials include

Self-interference fluorescence microscopy: three dimensional fluorescence imaging without depth scanning

We present a new method for high-resolution, three-dimensional fluorescence imaging. In contrast to beam-scanning confocal microscopy, where the laser focus must be scanned both laterally and axially to collect a volume, we obtain depth information without the necessity of depth scanning. In this method, the emitted fluorescence is collected in the backward direction and is sent through a phase plate that encodes the depth information into the phase of a spectrally resolved interference pattern. We demonstrate that decoding this phase information allows for depth localization accuracy better than 4 µm over a 500 µm depth-of-field. In a high numerical aperture configuration with a much smaller depth of field, a localization accuracy of tens of nanometers can be achieved. This approach is ideally suited for miniature endoscopes, where space limitations at the endoscope tip render depth scanning difficult. We illustrate the potential for 3D visualization of complex biological samples by constructing a three-dimensional volume of the microvasculature of ex vivo murine heart tissue from a single 2D scan

Spectral-domain optical coherence reflectometric sensor for highly sensitive molecular detection

We describe what we believe to be a novel use of spectral-domain optical coherence reflectometry (SD-OCR) for highly sensitive molecular detection in real time. The SD-OCR sensor allows identification of a sensor surface of interest in an OCR depth scan and monitoring the phase alteration due to molecular interaction at that surface with subnanometer optical thickness sensitivity. We present subfemtomole detection sensitivity for etching of Si

Peripapillary Retinal Thickness Maps in the Evaluation of Glaucoma Patients: A Novel Concept

Purpose. To show how peripapillary spectral domain optical coherence tomography (SDOCT) retinal thickness (RT) maps can complement retinal nerve fiber layer (RNFL) thickness maps in the evaluation of glaucoma patients. Methods:. After a complete eye exam with standard fundus photography and visual field testing, normal and glaucomatous eyes were imaged with an experimental SDOCT system. From SDOCT images, RNFL thickness and RT maps were constructed and then correlated with disc photography and visual field testing. Results:. Two normal eyes of 2 patients and 5 eyes of 4 glaucoma patients were imaged. Although both RNFL and RT maps correlated well with visual field defects, glaucomatous arcuate defects were sometimes more easily identified in the RT maps. Conclusions:. To our knowledge, this is the first paper to show that peripapillary SDOCT RT maps may provide important supplemental information to RNFL thickness maps in the evaluation of glaucoma patients

Robustness of Light-Transport Processes to Bending Deformations in Graded-Index Multimode Waveguides

Light transport through a multimode optical waveguide undergoes changes when subjected to bending deformations. We show that optical waveguides with a perfectly parabolic refractive index profile are almost immune to bending, conserving the structure of propagation-invariant modes. Moreover, we show that changes to the transmission matrix of parabolic-index fibers due to bending can be expressed with only two free parameters, regardless of how complex a particular deformation is. We provide detailed analysis of experimentally measured transmission matrices of a commercially available graded-index fiber as well as a gradient-index rod lens featuring a very faithful parabolic refractive index profile. Although parabolic-index fibers with a sufficiently precise refractive index profile are not within our reach, we show that imaging performance with standard commercially available graded-index fibers is significantly less influenced by bending deformations than step-index types under the same conditions. Our work thus predicts that the availability of ultraprecise parabolic-index fibers will make endoscopic applications with flexible probes feasible and free from extremely elaborate computational challenges

Robustness of Light-Transport Processes to Bending Deformations in Graded-Index Multimode Waveguides

Light transport through a multimode optical waveguide undergoes changes when subjected to bending deformations. We show that optical waveguides with a perfectly parabolic refractive index profile are almost immune to bending, conserving the structure of propagation-invariant modes. Moreover, we show that changes to the transmission matrix of parabolic-index fibers due to bending can be expressed with only two free parameters, regardless of how complex a particular deformation is. We provide detailed analysis of experimentally measured transmission matrices of a commercially available graded-index fiber as well as a gradient-index rod lens featuring a very faithful parabolic refractive index profile. Although parabolic-index fibers with a sufficiently precise refractive index profile are not within our reach, we show that imaging performance with standard commercially available graded-index fibers is significantly less influenced by bending deformations than step-index types under the same conditions. Our work thus predicts that the availability of ultraprecise parabolic-index fibers will make endoscopic applications with flexible probes feasible and free from extremely elaborate computational challenges

High resolution combined molecular and structural optical imaging of colorectal cancer in a xenograft mouse model

With the emergence of immunotherapies for cancer treatment, there is a rising clinical need to visualize the tumor microenvironment (TME) non-invasively in detail, which could be crucial to predict the efficacy of therapy. Nuclear imaging techniques enable whole-body imaging but lack the required spatial resolution. Conversely, near-infrared immunofluorescence (immuno-NIRF) is able to reveal tumor cells and/or other cell subsets in the TME by targeting the expression of a specific membrane receptor with fluorescently labeled monoclonal antibodies (mAb). Optical coherence tomography (OCT) provides three-dimensional morphological imaging of tissues without exogenous contrast agents. The combination of the two allows molecular and structural contrast at a resolution of ~15 µm, allowing for the specific location of a cell-type target with immuno-NIRF as well as revealing the three-dimensional architectural context with OCT. For the first time, combined immuno-NIRF and OCT of a tumor is demonstrated in situ in a xenograft mouse model of human colorectal cancer, targeted by a clinically-safe fluorescent mAb, revealing unprecedented details of the TME. A handheld scanner for ex vivo examination and an endoscope designed for imaging bronchioles in vivo are presented. This technique promises to complement nuclear imaging for diagnosing cancer invasiveness, precisely determining tumor margins, and studying the biodistribution of newly developed antibodies in high detail

Spectral-domain optical coherence phase and multiphoton microscopy

We describe simultaneous quantitative phase contrast and multiphoton fluorescence imaging by combined spectral-domain optical coherence phase and multiphoton microscopy. The instrument employs two light sources for efficient optical coherence microscopic and multiphoton imaging and can generate structural and functional images of transparent specimens in the epidirection. Phase contrast imaging exhibits spatial and temporal phase stability in the subnanometer range. We also demonstrate the visualization of actin filaments in a fixed cell specimen, which is confirmed by simultaneous multiphoton fluorescence imaging. © 2007 Optical Society of America