David P. Klemer

Design and implementation of dynamic near-infrared optical tomographic imaging instrumentation for simultaneous dual-breast measurements

Dynamic near-infrared optical tomographic measurement instrumentation capable of simultaneous bilateral breast imaging, having a capability of four source wavelengths and 32 source-detector fibers for each breast, is described. The system records dynamic optical data simultaneously from both breasts, while verifying proper optical fiber contact with the tissue through implementation of automatic schemes for evaluating data integrity. Factors influencing system complexity and performance are discussed, and experimental measurements are provided to demonstrate the repeatability of the instrumentation. Considerations in experimental design are presented, as well as techniques for avoiding undesirable measurement artifacts, given the high sensitivity and dynamic range (1:10(9)) of the system. We present exemplary clinical results comparing the measured physiologic response of a healthy individual and of a subject with breast cancer to a Valsalva maneuver.

Selenomethionine reduces visual deficits due to developmental methylmercury exposures

Developmental exposures to methylmercury (MeHg) have life-long behavioral effects. Many micronutrients, including selenium, are involved in cellular defenses against oxidative stress and may reduce the severity of MeHg-induced deficits. Zebrafish embryos (<4 h post fertilization, hpf) were exposed to combinations of 0.0-0.30 microM MeHg and/or selenomethionine (SeMet) until 24 hpf then placed in clean medium. Fish were tested as adults under low light conditions ( approximately 60 microW/m(2)) for visual responses to a rotating black bar. Dose-dependent responses to MeHg exposure were evident (ANOVA, P<0.001) as evidenced by reduced responsiveness, whereas SeMet did not induce deficits except at 0.3 microM. Ratios of SeMet:MeHg of 1:1 or 1:3 resulted in responses that were indistinguishable from controls (ANOVA, P<0.001). No gross histopathologies were observed (H&E stain) in the retina or optic tectum at any MeHg concentration. Whole-cell, voltage-gated, depolarization-elicited outward K(+) currents of bipolar cells in intact retina of slices adult zebrafish were recorded and outward K(+) current amplitude was larger in bipolar cells of MeHg-treated fish. This was due to the intense response of cells expressing the delayed rectifying I(K) current; cells expressing the transient I(A) current displayed a slight trend for smaller amplitude among MeHg-treated fish. Developmental co-exposure to SeMet reduced but did not eliminate the increase in the MeHg-induced I(K) response, however, I(A) responses increased significantly over MeHg-treated fish to match control levels. Electrophysiological deficits parallel behavioral patterns in MeHg-treated fish, i.e., initial reactions to the rotating bar were followed by periods of inactivity and then a resumption of responses.

Fabrication and characterization of microwave immunosensors based on organic semiconductors with nanogold-labeled antibody

Microelectronic biosensors hold great promise for rapid, sensitive and specific in vitro point-of-care immunodiagnostics. In particular, sensors fabricated using organic semiconductors have attractive advantages—such as ease of manufacture and low cost—in the design and implementation of such devices. Furthermore, immobilization of an antibody or protein antigen as a biorecognition element onto an organic semiconducting film allows for direct transduction of biomolecular binding events into an electronic signal which is readily measured and processed. In previous work, we have demonstrated that an antigen can be bound to organic semiconducting films while retaining enzymatic activity after immobilization. The present work considers organic semiconducting films which are spin-cast onto an interdigitated electrode; antibodies labeled with gold-nanoparticles are applied to the organic semiconducting film and serve as a biorecognition element. The sensor geometry includes a high-frequency coplanar waveguide contact metallization to facilitate direct measurement using microwave wafer probes. Equivalent circuit models are derived from microwave measurements over the frequency range 0.3 MHz to 8.5 GHz.

Determination of Fiber Orientation in MRI Diffusion Tensor Imaging Based on Higher-Order Tensor Decomposition

High angular resolution diffusion imaging (HARDI) techniques have been used for resolving multiple fiber directions within a voxel. Using HARDI, a high-order tensor can be obtained through generalized diffusion tensor imaging (GDTI). In this paper, based on the decomposition of the high-order diffusion tensors, a mathematical technique is presented which permits accurate resolution of multiple, randomly-oriented fiber tracts within tissue. A sequence of pseudo-eigenvalues and pseudo-eigenvectors are derived from the diffusion tensor through successive application of a best least-square rank-1 tensor approximation. These pseudo-eigenvalues and pseudo-eigenvectors are used to identify the major fiber directions within an individual image voxel. Results of a numerical simulation are presented to demonstrate the technique.

Two-dimensional dielectric imaging for dermatologic screening: a feasibility study

The diagnosis of skin neoplasia can be very challenging, given the low sensitivity and specificity of traditional methods of diagnosis which are based on visual appearance. Techniques which are based on the dielectric properties of cells can improve the diagnostic accuracy of screening techniques; as an example, point‐contact coaxial probes for dielectric measurement can improve diagnostic accuracy. Unfortunately, these probes are not well suited for two‐dimensional spatial imaging of the skin surface, given that they must be manually scanned over the skin surface.

Implementation of a fast reconfigurable array for tissue impedance characterization

Various tissue properties have been used in the past and present as metrics which can serve to discriminate healthy from diseased tissue. Electromagnetic absorption (of x-rays and optical signals), scattering of near-infrared light, and electrical impedance are a few such parameters. In order to serve as discriminants for diseased (e.g., neoplastic) tissue, the characteristics of these tissues must first be precisely determined. In this paper, we consider the electrical impedance properties of tissues and cell aggregates, and present the design of a reconfigurable electrode array which is capable of providing a well-defined electromagnetic interface to the tissue under study, for characterization in the 0.01–30 MHz range. The configuration of array elements may be easily changed under digital control, allowing for various electromagnetic field configurations to be applied to the tissue under study. The array is designed to interface to four-point as well as two-point impedance instrumentation, and may be used for two-dimensional bioimaging systems based on electrical impedances. The design may be scaled to higher frequencies and smaller dimensions, allowing for studies of electrical properties at the cellular level.

Fabrication of Polydimethylsiloxane Phantoms for Optical Imaging Based on Quantum Dot Nanofluorophores

We describe a method for fabrication of polydimethy lsiloxane (PDMS) phantoms suitable for optical fluorescence imaging systems based on quantum dot nanofluorophores in aqueous solution, and illustrate examples of phantom designs and measurements.

Evaluation of peripheral vascular disease using non-invasive dynamic optical tomography

Using dynamic optical tomography, we observed a difference in metabolic usage of oxygen and in vascular reactivity during and after provocative tests in the limbs of healthy and diabetic patients.

Multi-site near-infrared tomographic imaging of the brain

Time-series analysis techniques are applied to dynamic near-infrared tomographic images of the motor and frontal cortex of the brain, based on optical data simultaneously recorded from two 3 x 5 arrays.

Design and initial testing of system for simultaneous bilateral dynamic optical tomographic mammography

The sensitivity of our previously published methods for breast cancer detection with dynamic optical tomography now has been significantly augmented, via the use of a measuring head that permits simultaneous bilateral data collection.