Monica J. Holboke

Three-dimensional diffuse optical tomography in the parallel plane transmission geometry: evaluation of a hybrid frequency domain/continuous wave clinical system for breast imaging.

Three-dimensional diffuse optical tomography (DOT) of breast requires large data sets for even modest resolution (1 cm). We present a hybrid DOT system that combines a limited number of frequency domain (FD) measurements with a large set of continuous wave (cw) measurements. The FD measurements are used to quantitatively determine tissue averaged absorption and scattering coefficients. The larger cw data sets (10(5) measurements) collected with a lens coupled CCD, permit 3D DOT reconstructions of a 1-liter tissue volume. To address the computational complexity of large data sets and 3D volumes we employ finite difference based reconstructions computed in parallel. Tissue phantom measurements evaluate imaging performance. The tests include the following: point spread function measures of resolution, characterization of the size and contrast of single objects, field of view measurements and spectral characterization of constituent concentrations. We also report in vivo measurements. Average tissue optical properties of a healthy breast are used to deduce oxy- and deoxy-hemoglobin concentrations. Differential imaging with a tumor simulating target adhered to the surface of a healthy breast evaluates the influence of physiologic fluctuations on image noise. This tomography system provides robust, quantitative, full 3D image reconstructions with the advantages of high data throughput, single detector-tissue coupling path, and large (1L) imaging domains. In addition, we find that point spread function measurements provide a useful and comprehensive representation of system performance.

Bulk optical properties of healthy female breast tissue

We have measured the bulk optical properties of healthy female breast tissues in vivo in the parallel plate, transmission geometry. Fifty-two volunteers were measured. Blood volume and blood oxygen saturation were derived from the optical property data using a novel method that employed a priori spectral information to overcome limitations associated with simple homogeneous tissue models. The measurements provide an estimate of the variation of normal breast tissue optical properties in a fairly large population. The mean blood volume was 34 +/- 9 microM and the mean blood oxygen saturation was 68 +/- 8%. We also investigated the correlation of these optical properties with demographic factors such as body mass index (BMI) and age. We observed a weak correlation of blood volume and reduced scattering coefficient with BMI: correlation with age, however, was not evident within the statistical error of these experiments. The new information on healthy breast tissue provides insight about the potential contrasts available for diffuse optical tomography of breast tumours.

Optimization of optode arrangements for diffuse optical tomography: A singular-value analysis

We develope a method to optimize the resolution of diffuse optical tomographic instruments. Singular-value analysis of the tomographic weight matrix associated with specific data types, geometries, and optode arrangements is shown to provide a measure of image resolution. We achieve optimization of device configuration by monitoring the resolution measure described. We introduce this idea and demonstrate its utility by optimizing the spatial sampling interval and field-of-view parameters in the parallel-plane transmission geometry employed for diffuse optical breast imaging. We also compare resolution in transmission and remission geometries.

Three-dimensional diffuse optical mammography with ultrasound localization in a human subject

We describe an approach that combines clinical ultrasound and photon migration techniques to enhance the sensitivity and information content of diffuse optical tomography. Measurements were performed on a postmenopausal woman with a single 1.8 x 0.9 cm malignant ductal carcinoma in situ approximately 7.4 mm beneath the skin surface (UCI IRB protocol 95-563). The ultrasound-derived information about tumor geometry enabled us to segment the breast tissue into tumor and background regions. Optical data was obtained with a multifrequency, multiwavelength hand-held frequency-domain photon migration backscattering probe. The optical properties of the tumor and background were then computed using the ultrasound-derived geometrical constraints. An iterative perturbative approach, using parallel processing, provided quantitative information about scattering and absorption simultaneously with the ability to incorporate and resolve complex boundary conditions and geometries. A three to four fold increase in the tumor absorption coefficient and nearly 50% reduction in scattering coefficient relative to background was observed (lambda = 674, 782, 803, and 849 nm). Calculations of the mean physiological parameters reveal fourfold greater tumor total hemoglobin concentration [Hbtot] than normal breast (67 microM vs 16 microM) and tumor hemoglobin oxygen saturation (SOx) values of 63% (vs 73% and 68% in the region surrounding the tumor and the opposite normal tissue, respectively). Comparison of semi-infinite to heterogeneous models shows superior tumor/background contrast for the latter in both absorption and scattering. Sensitivity studies assessing the impact of tumor size and refractive index assumptions, as well as scan direction, demonstrate modest effects on recovered properties.

Imager that combines near-infrared diffusive light and ultrasound

We introduce an imaging technique that combines complementary features of ultrasound and near-infrared diffusive light imaging. We achieve the combined technology experimentally by mounting an ultrasound array together with multiple laser source and optical detector fibers upon a hand-held probe. The technique is demonstrated with tissue phantoms wherein both acoustic and optical sensors image the volume underneath the probe. Coregistration of acoustic and optical images is achieved with an accuracy of 0.27+/-0.20cm, approximately half of the image pixel size of our prototype. Accurate determination of target optical absorption is also achieved by use of image segmentation on the ultrasound reconstruction. The combined technique may provide improved breast-cancer detection sensitivity and specificity.

Interfering diffusive photon-density waves with an absorbing-fluorescent inhomogeneity

This work reports an investigation of the fluorescent field re-emitted by an object embedded in a highly scattering media illuminated by two-interfering sources. Simulations in the frequency domain with a finite difference method solving the diffusion equation were performed. The media considered had features typical of a soft-compressed breast. An absorbing-fluorescent inhomogeneity was embedded in the center of the slab. A qualitative study of the re-emitted field was achieved. The re-emitted field was found to possess unique features characteristic of the two-interfering sources excitation, i.e. null intensity when the object was between the two sources and a 180 degrees transition crossing this position. Those features, when performing a scan of the two sources, permitted accurate localization of the inhomogeneity. Moreover, even when the detector was not placed on the mid-plane of the two sources, the re-emitted field still exhibited the interfering characteristic pattern, which was not seen at the excitation wavelength. Thus, for such configurations, the re-emitted field still possessed the specific sensitivity of phased array emission conversely to the excitation wavelength.

Algorithms for 3D localization and imaging using near-field diffraction tomography with diffuse light

We introduce two filtering methods for near-field diffuse light diffraction tomography based on the angular spectrum representation. We then combine these filtering techniques with a new method to find the approximate depth of the image heterogeneities. Taken together these ideas improve the fidelity of our projection image reconstructions, provide an interesting three dimensional rendering of the reconstructed volume, and enable us to identify and classify image artifacts that need to be controlled better for tissue applications. The analysis is accomplished using data derived from numerical finite difference simulations with added noise.

Optimal selection of frequencies for diffuse optical tomography

The use of diffuse photon density waves (DPDW) at multiple modulation frequencies is a significant tool for Diffuse Optical Tomography (DOT). Use of higher frequencies offers higher contrast between scattering and absorbing objects and allows higher resolution to be achieved. Here we focus on the optimal use of frequencies in simultaneously resolving absorbing and scattering objects using simulated data.

Detection sensitivity and optimization of a phased-array system

Previous studies have suggested that the phased-array detection could achieve high sensitivity in detecting and localizing inhomogeneity embedded within turbid media by applying dual interfering sources. While the sensitivity of the phased array system will be influenced by various factors such as the source-detector configuration, the effect of noises (variation of source strength and phase, detector noise, imperfect homogeneous medium, etc.) and the modulation frequency. Analytical solutions as well as experimental data are presented to investigate the sensitivity of phased array detection using different degrees of absorption perturbation by varying the size and contrast of the absorber. Also we compare the result with the single source case under similar configuration. Different separations between two interfering sources have been compared to yield the maximum sensitivity for a typical perturbation. These results can be helpful for modifying the experimental apparatus to reach optimal detection sensitivity.

Dual interfering sources with a fluorescent object

The properties of the field re-emitted by an absorbing- fluorescent object embedded in a highly scattering media excited by a dual-interfering sources system are investigated. The geometry considered is transmission geometry with a breast like phantom. This study is based on simulations performed in the frequency domain with a finite difference method to solve the diffusion equation. The fluorescent detected field possessed the features of the interfering excitation pattern. This specific pattern allows to accurately localization of the inhomogeneity.