Yaling Pei

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.

Frequency-domain optical imaging of absorption and scattering distributions by a Born iterative method

We presents a Born; iterative method, for reconstructing optical properties of turbid media by means of frequency-domain data. The approach is based on iterative solution of a linear perturbation equation, which is derived from the integral from of the Helmholtz wave equation for photon-density waves in each iteration the total field and the associated weight matrix are recalculated based on the previous reconstructed image. We then obtain a new estimate by solving the updated perturbation equation. The forward solution, also based on a Helmholtz equation, is obtained by a multigrid finite difference method. The inversion is carried out through a Tikhonov regularized optimization process by the conjugate gradient descent method. Using this method, we first reconstruct the distribution of the complex wave numbers in a test medium, from which the absorption and the scattering distributions are then derived. Simulation results with two-dimensional test media have shown that this method can yield quantitatively (in terms of coefficient valued) as well as qualitatively (in terms of object location and shape) accurate reconstructions of absorption and scattering distributions in cases in which the first-order Born approximation cannot work well. Both full-angle and limited-angle measurement schemes have been simulated to examine the effect of the location of detectors and sources. The robustness of the algorithm to noise has also been evaluated.

Instrumentation and calibration protocol for imaging dynamic features in dense-scattering media by optical tomography

Instrumentation is described that is suitable for acquiring multisource, multidetector, time-series optical data at high sampling rates (up to 150 Hz) from tissues having arbitrary geometries. The design rationale, calibration protocol, and measured performance features are given for both a currently used, CCD-camera-based instrument and a new silicon-photodiode-based system under construction. Also shown are representative images that we reconstructed from data acquired in laboratory studies using the described CCD-based instrument.

Influence of systematic errors in reference states on image quality and on stability of derived information for dc optical imaging

Optical measurements of tissue can be performed in discrete, time-averaged, and time-varying data collection modes. This information can be evaluated to yield estimates of either absolute optical coefficient values or some relative change in these values compared with a defined state. In the case of time-varying data, additional analysis can be applied to define various dynamic features. Here we have explored the accuracy with which such information can be recovered from dense scattering media using linear perturbation theory, as a function of the accuracy of the reference medium that serves as the initial guess. Within the framework of diffusion theory and a first-order solution, we have observed the following inequality regarding the sensitivity of computed measures to inaccuracy in the reference medium: Absolute measures ? relative measures > dynamic measures. In fact, the fidelity of derived dynamic measures was striking; we observed that accurate measures of dynamic behavior could be defined even if the quality of the image data from which these measures were derived was comparatively modest. In other studies we identified inaccuracy in the estimates of the reference detector values, and not to corresponding errors in the image operators, as the primary factor responsible for instability of absolute measures. The significance of these findings for practical imaging studies of tissue is discussed.

Normalized–constraint algorithm for minimizing inter–parameter crosstalk in DC optical tomography

In this report, we present a method for reducing the inter-coefficient crosstalk problem in optical tomography. The method described is an extension of a previously reported normalized difference method that evaluates relative detector values, and employs a weight matrix scaling technique together with a constrained CGD method for image reconstruction. Results from numerical and experimental studies using DC measurement data demonstrate that the approach can effectively isolate absorption and scattering heterogeneities, even for complex combinations of perturbations in optical properties. The significance of these results in light of recent theoretical findings is discussed.

Using co-variations in the Hb signal to detect visual activation: A near infrared spectroscopic imaging study

The premise of this report is that functional Near Infrared Spectroscopy (fNIRS) imaging data contain valuable physiological information that can be extracted by using analysis techniques that simultaneously consider the components of the measured hemodynamic response [i.e., levels of oxygenated, deoxygenated and total hemoglobin (oxyHb, deoxyHb and totalHb, respectively)]. We present an algorithm for examining the spatiotemporal co-variations among the Hb components, and apply it to the data obtained from a demonstrational study that employed a well-established visual stimulation paradigm: a contrast-reversing checkerboard. Our results indicate that the proposed method can identify regions of tissue that participate in the hemodynamic response to neuronal activation, but are distinct from the areas identified by conventional analyses of the oxyHb, deoxyHb and totalHb data. A discussion is provided that compares these findings to other recent studies using fNIRS techniques.

Imaging of spatiotemporal coincident states by DC optical tomography

The utility of optical tomography as a practical imaging modality has, thus far, been limited by its intrinsically low spatial resolution and quantitative accuracy. Recently, we have argued that a broad range of physiological phenomena might be accurately studied by adopting this technology to investigate dynamic states (Schmitz et al., 2000; Barbour et al., 2000; Graber et al., 2000; Barbour et al., 2001; and Barbour et al., 1999). One such phenomenon holding considerable significance is the dynamics of the vasculature, which has been well characterized as being both spatially and temporally heterogeneous. In this paper, we have modeled such heterogeneity in the limiting case of spatiotemporal coincident behavior involving optical contrast features, in an effort to define the expected limits with which dynamic states can be characterized using two newly described reconstruction methods that evaluate normalized detector data: the normalized difference method (NDM) and the normalized constraint method (NCM). Influencing the design of these studies is the expectation that spatially coincident temporal variations in both the absorption and scattering properties of tissue can occur in vivo. We have also chosen to model DC illumination techniques, in recognition of their favorable performance and cost for practical systems. This choice was made with full knowledge of theoretical findings arguing that separation of the optical absorption and scattering coefficients under these conditions is not possible. Results obtained show that the NDM algorithm provides for good spatial resolution and excellent characterization of the temporal behavior of optical properties but is subject to interparameter crosstalk. The NCM algorithm, while also providing excellent characterization of temporal behavior, provides for improved spatial resolution, as well as for improved separation of absorption and scattering coefficients. A discussion is provided to reconcile these findings with theoretical expectations.

Clinical applications of dynamic optical tomography in vascular disease

Vascular disease is a significant source of mortality and morbidity for many patient populations. While substantial strides in surgical therapeutics have been made in the past decade, our limited understanding of the microvascular processes, which are invisible to conventional imaging modalities and beyond the scope of our current physiologic paradigms, has slowed the advancement of medical therapeutic interventions. In this report we present data in support of an emerging body of work demonstrating that the method of dynamic optical tomography can yield critical insights into the underpinnings of microvascular pathophysiology in large tissue structures.

Dynamic studies of small animals with a four-color diffuse optical tomography imager

We present newly developed instrumentation for full-tomographic four-wavelength, continuous wave, diffuse optical tomography (DOT) imaging on small animals. A small-animal imaging stage was constructed, from materials compatible with in-magnet studies, which offers stereotaxic fixation of the animal and precise, stable probe positioning. Instrument performance, based on calibration and phantom studies, demonstrates excellent long-term signal stability. DOT measurements of the functional rat brain response to electric paw stimulation are presented, and these demonstrate high data quality and excellent sensitivity to hemodynamic changes. A general linear model analysis on individual trials is used to localize and quantify the occurrence of functional behavior associated with the different hemoglobin state responses. Statistical evaluation of outcomes of individual trials is employed to identify significant regional response variations for different stimulation sites. Image results reveal a diffuse cortical ...

A Programmable Laboratory Testbed in Support of Evaluation of Functional Brain Activation and Connectivity

An important determinant of the value of quantitative neuroimaging studies is the reliability of the derived information, which is a function of the data collection conditions. Near infrared spectroscopy (NIRS) and electroencelphalography are independent sensing domains that are well suited to explore principal elements of the brains response to neuroactivation, and whose integration supports development of compact, even wearable, systems suitable for use in open environments. In an effort to maximize the translatability and utility of such resources, we have established an experimental laboratory testbed that supports measures and analysis of simulated macroscopic bioelectric and hemodynamic responses of the brain. Principal elements of the testbed include 1) a programmable anthropomorphic head phantom containing a multisignal source array embedded within a matrix that approximates the background optical and bioelectric properties of the brain, 2) integrated translatable headgear that support multimodal studies, and 3) an integrated data analysis environment that supports anatomically based mapping of experiment-derived measures that are directly and not directly observable. Here, we present a description of system components and fabrication, an overview of the analysis environment, and findings from a representative study that document the ability to experimentally validate effective connectivity models based on NIRS tomography.