Vaibhav Gaind

Deep-tissue imaging of intramolecular fluorescence resonance energy-transfer parameters

We demonstrate the in vivo reconstruction of all fluorescence resonance energy transfer (FRET) parameters, including the nanometer donor-acceptor distance, in a mouse. The FRET chemical targets cancer cells, and on internalization, the acceptor is released, in lieu of a targeted anticancer drug in chemotherapy. Our method provides a new vehicle for studying disease by imaging FRET parameters in deep tissue.

Prediction of electric field frequency correlations for randomly scattering slabs in the nondiffusive regime with the scalar Bethe–Salpeter equation

We show that a scalar Bethe-Salpeter equation model captures the measured copolarized electric field frequency correlation magnitude for randomly scattering slabs in the weakly scattering, nondiffusive regime. Consequently, the model could be used to form images of tissue on the millimeter and submillimeter length scale, and for environmental sensing with comparable scatter, as dictated by the optical scattering length in relation to the scattering domain size.

In vivo mouse fluorescence imaging for folate-targeted delivery and release kinetics.

Many cancer cells over-express folate receptors, and this provides an opportunity for both folate-targeted fluorescence imaging and the development of targeted anti-cancer drugs. We present an optical imaging modality that allows for the monitoring and evaluation of drug delivery and release through disulfide bond reduction inside a tumor in vivo for the first time. A near-infrared folate-targeting fluorophore pair was synthesized and used to image a xenograft tumor grown from KB cells in a live mouse. The in vivo results are shown to be in agreement with previous in vitro studies, confirming the validity and feasibility of our method as an effective tool for preclinical studies in drug development.

Small animal optical diffusion tomography with targeted fluorescence

Despite the broad impact in medicine that optics can bring, thus far practical approaches are limited to weak scatter or near-surface monitoring. We show a method that utilizes a laser topography scan and a diffusion equation model to describe the photon transport, together with a multiresolution unstructured grid solution to the nonlinear optimization measurement functional, that overcomes these limitations. We conclude that it is possible to achieve whole body optical imaging with a resolution suitable for finding cancer nodules within an organ during surgery, with the aid of a targeted imaging agent.

Localization of an absorbing inhomogeneity in a scattering medium in a statistical framework

An approach for the fast localization and detection of an absorbing inhomogeneity in a tissuelike scattering medium is presented. The probability of detection as a function of the size, location, and absorptive properties of the inhomogeneity is investigated. The detection sensitivity in relation to the source and detector location serves as a basis for instrument design.

Momentum-resolved Electron Energy Loss Spectroscopy (q-EELS) for Quantum Plasmonics and Metamaterials

We report on experimental and theoretical results on EELS from 12nm single-crystal gold films. Our results show that momentum resolution of the electrons gives insight into signatures of non-locality and quantum nature of the excitations.

In Vivo Fluorescence Imaging for Folate-Targeted Kinetics

We demonstrate the in vivo imaging of a mouse tumor using fluorescence optical diffusion tomography and the extraction of kinetic information from a compartment model, yielding the first folate drug release kinetics inside cancer cells.

In Vivo Optical Imaging of Kinetics in a Small Animal for Folate-Targeted Drug Development

The delivery and release of folate-targeted anti-cancer drugs has been largely unknown, inhibiting drug development. We show how to access this information and illustrate this with in vivo mouse images of fluorophore pair release kinetics.

Solution of the Bethe–Salpeter equation in a nondiffusive random medium having large scatterers

We present a formalism for solving the scalar Bethe–Salpeter equation (BSE) in the nondiffusive regime under the ladder approximation and for an infinite randomly scattering medium having scatterers of size on the order of or larger than the wavelength. We compare the information content in a wave transport model (the BSE) with that in energy-based transport, the Boltzmann transport equation (BTE), in the spatial frequency domain. Our results suggest that when absorption dominates scatter, the intensity Green’s function from a BTE model is similar to the field correlation Green’s function from a BSE solution. When scatter dominates loss, there are significant differences between the BTE and BSE representations, and the BTE solutions appear to be smoothed versions of those from the BSE. Therefore, field correlation measurements, perhaps extracted from intensity correlations over frequency and space, offer significantly more information than a mean-intensity measurement in the weakly scattering and nondiffusive regime. Our work provides a mathematical framework for electric field correlation-based imaging methods based on the BSE that hold promise in, for example, near-surface tissue imaging.

Imaging fluorescence resonance energy transfer in scattering media using optical diffusion tomography

We present experiments and simulations that show the microscopic fluorescence resonance energy transfer (FRET) donor-acceptor distance can be determined using a diffusion model. The approach could lead to deep tissue in-vivo FRET imaging.