Simultaneous imaging of a lacZ-marked tumor and microvasculature morphology in vivo by dual-wavelength photoacoustic microscopy

Photoacoustic molecular imaging, combined with the reporter-gene technique, can provide a valuable tool for cancer research. The expression of the lacZ reporter gene can be imaged using photoacoustic imaging following the injection of X-gal, a colorimetric assay for the lacZ-encoded enzyme β-galactosidase. Dual-wavelength photoacoustic microscopy was used to non-invasively image the detailed morphology of a lacZ-marked 9L gliosarcoma and its surrounding microvasculature simultaneously in vivo, with a superior resolution on the order of 10 μm. Tumor-feeding vessels were found, and the expression level of lacZ in tumor was estimated. With future development of new absorption-enhancing reporter-gene systems, we anticipate this strategy can lead to a better understanding of the role of tumor metabolism in cancer initiation, progression, and metastasis, and in its response to therapy

Label-free high-throughput photoacoustic tomography of suspected circulating melanoma tumor cells in patients in vivo

Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention. Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs. Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans. Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression. Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma

Inverse Problems in Wave Scattering

The workshop treated inverse problems for partial differential equations, especially inverse scattering problems, and their applications in technology. While special attention was paid to sampling methods, decomposition methods, Newton methods and questions of unique determination were also investigated

Diffusive tomography methods : special boundary conditions and characterization of inclusions

This thesis presents mathematical analysis of optical and electrical impedance tomography. We introduce papers [I-III], which study these diffusive tomography methods in the situation where the examined object is contaminated with inclusions that have physical properties differing from the background.reviewe

Diffuse Optical Imaging Using Decomposition Methods

Diffuse optical imaging (DOI) for detecting and locating targets in a highly scattering turbid medium is treated as a blind source separation (BSS) problem. Three matrix decomposition methods, independent component analysis (ICA), principal component analysis (PCA), and nonnegative matrix factorization (NMF) were used to study the DOI problem. The efficacy of resulting approaches was evaluated and compared using simulated and experimental data. Samples used in the experiments included Intralipid-10% or Intralipid-20% suspension in water as the medium with absorptive or scattering targets embedded

Deeply penetrating in vivo photoacoustic imaging using a clinical ultrasound array system

Using a hand-held photoacoustic probe integrated with a clinical ultrasound array system, we successfully imaged objects deeply positioned in biological tissues. The optical contrasts were enhanced by methylene blue with a concentration of ~30 mM. The penetration depth reached ~5.2 cm in chicken breast tissue by using 650-nm wavelength, which is ~4.7 times the 1/e optical penetration depth. This imaging depth was achieved using a laser fluence on the tissue surface of only 3 mJ/cm2, which is 1/7 of the American National Standards Institute (ANSI) safety limit (20 mJ/cm2). The noise equivalent sensitivity at this depth was ~11 mM. Further, after intradermal injection of methylene blue in a rat, a sentinel lymph node was easily detected in vivo, beneath a 2-cm thick layer of chicken breast. Also, blood located 3.5 cm deep in the rat was clearly imaged with intrinsic contrast. We have photoacoustically guided insertion of a needle into a rat sentinel lymph node with accumulated methylene blue. These results highlight the clinical potential of photoacoustic image-guided identification and needle biopsy of sentinel lymph nodes for axillary staging in breast cancer patients

Hybrid-dual-fourier tomographic algorithm for a fast three-dimensionial optical image reconstruction in turbid media

A reconstruction technique for reducing computation burden in the 3D image processes, wherein the reconstruction procedure comprises an inverse and a forward model. The inverse model uses a hybrid dual Fourier algorithm that combines a 2D Fourier inversion with a 1D matrix inversion to thereby provide high-speed inverse computations. The inverse algorithm uses a hybrid transfer to provide fast Fourier inversion for data of multiple sources and multiple detectors. The forward model is based on an analytical cumulant solution of a radiative transfer equation. The accurate analytical form of the solution to the radiative transfer equation provides an efficient formalism for fast computation of the forward model

Coherent microscopy by laser optical feedback imaging (LOFI) technique

The application of the non conventional imaging technique LOFI (Laser Optical Feedback Imaging) to coherent microscopy is presented. This simple and efficient technique using frequency-shifted optical feedback needs the sample to be scanned in order to obtain an image. The effects on magnitude and phase signals such as vignetting and field curvature occasioned by the scanning with galvanometric mirrors are discussed. A simple monitoring method based on phase images is proposed to find the optimal position of the scanner. Finally, some experimental results illustrating this technique are presented

High-density diffuse optical tomography for imaging human brain function

This review describes the unique opportunities and challenges for noninvasive optical mapping of human brain function. Diffuse optical methods offer safe, portable, and radiation free alternatives to traditional technologies like positron emission tomography or functional magnetic resonance imaging (fMRI). Recent developments in high-density diffuse optical tomography (HD-DOT) have demonstrated capabilities for mapping human cortical brain function over an extended field of view with image quality approaching that of fMRI. In this review, we cover fundamental principles of the diffusion of near infrared light in biological tissue. We discuss the challenges involved in the HD-DOT system design and implementation that must be overcome to acquire the signal-to-noise necessary to measure and locate brain function at the depth of the cortex. We discuss strategies for validation of the sensitivity, specificity, and reliability of HD-DOT acquired maps of cortical brain function. We then provide a brief overview of some clinical applications of HD-DOT. Though diffuse optical measurements of neurophysiology have existed for several decades, tremendous opportunity remains to advance optical imaging of brain function to address a crucial niche in basic and clinical neuroscience: that of bedside and minimally constrained high fidelity imaging of brain function