Kijoon Lee

Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI.

We employ diffuse optical tomography (DOT) to track treatment progress in a female subject presenting with locally advanced invasive carcinoma of the breast during neoadjuvant chemotherapy. Three-dimensional images of total hemoglobin concentration and scattering identified the tumor. Our measurements reveal tumor shrinkage during the course of chemotherapy, in reasonable agreement with magnetic resonance images of the same subject. A decrease in total hemoglobin concentration contrast between tumor and normal tissue was also observed over time. The results demonstrate the potential of DOT for measuring physiological parameters of breast lesions during chemotherapy.

Diffuse optical tomography with spectral constraints and wavelength optimization

We present an algorithm that explicitly utilizes the wavelength dependence of tissue optical properties for diffuse optical tomography. We have previously shown that the method gives superior separation of absorption and scattering. Here the technique is described and tested in detail, and optimum wavelength sets for a broad range of chromophore combinations are discovered and analyzed.

Imaging complex structures with diffuse light.

We use diffuse optical tomography to quantitatively reconstruct images of complex phantoms with millimeter sized features located centimeters deep within a highly-scattering medium. A non-contact instrument was employed to collect large data sets consisting of greater than 10(7) source-detector pairs. Images were reconstructed using a fast image reconstruction algorithm based on an analytic solution to the inverse scattering problem for diffuse light.

Comparison of diffuse optical tomography of human breast with whole‐body and breast‐only positron emission tomography

We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.

Standardized platform for coregistration of nonconcurrent diffuse optical and magnetic resonance breast images obtained in different geometries

We present a novel methodology for combining breast image data obtained at different times, in different geometries, and by different techniques. We combine data based on diffuse optical tomography (DOT) and magnetic resonance imaging (MRI). The software platform integrates advanced multimodal registration and segmentation algorithms, requires minimal user experience, and employs computationally efficient techniques. The resulting superposed 3-D tomographs facilitate tissue analyses based on structural and functional data derived from both modalities, and readily permit enhancement of DOT data reconstruction using MRI-derived a-priori structural information. We demonstrate the multimodal registration method using a simulated phantom, and we present initial patient studies that confirm that tumorous regions in a patient breast found by both imaging modalities exhibit significantly higher total hemoglobin concentration (THC) than surrounding normal tissues. The average THC in the tumorous regions is one to three standard deviations larger than the overall breast average THC for all patients.

Quantitative comparison of tissue oxygen and motexafin lutetium uptake by ex vivo and noninvasive in vivo techniques in patients with intraperitoneal carcinomatosis

Near-infrared diffuse reflectance spectroscopy (DRS) has been used to noninvasively monitor optical properties during photodynamic therapy (PDT). This technique has been extensively validated in tissue phantoms; however, validation in patients has been limited. This pilot study compares blood oxygenation and photosensitizer tissue uptake measured by multiwavelength DRS with ex vivo assays of the hypoxia marker, 2-(2-nitroimida-zol-1[H]-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide (EF5), and the photosensitizer (motexafin lutetium, MLu) from tissues at the same tumor site of three tumors in two patients with intra-abdominal cancers. Similar in vivo and ex vivo measurements of MLu concentration are carried out in murine radiation-induced fibrosarcoma (RIF) tumors (n=9). The selection of optimal DRS wavelength range and source-detector separations is discussed and implemented, and the association between in vivo and ex vivo measurements is examined. The results demonstrate a negative correlation between blood oxygen saturation (StO(2)) and EF5 binding, consistent with published relationships between EF5 binding and electrode measured pO(2), and between electrode measured pO(2) and StO(2). A tight correspondence is observed between in vivo DRS and ex vivo measured MLu concentration in the RIF tumors; similar data are positively correlated in the human intraperitoneal tumors. These results further demonstrate the potential of in vivo DRS measurements in clinical PDT.

Transmission RF diffuse optical tomography instrument for human breast imaging

In this paper, we describe a novel clinical breast diffuse optical tomography (DOT) instrument for CW and RF data acquisition in transmission geometry. It is designed to be able to acquire a massive amount of data in a short amount of time available for patient measurement by using a 209-channel galvo-based fast optical switch and a fast electron-multiplying CCD. In addition to CW measurements, RF measurements were made by using an electro-optic modulator for source modulation and a gain-modulated image intensifier for detection. The patient bed has many clinically-oriented features as well as improved data acquisition rate and transmission RF measurement capability. A series of preliminary results will be shown, including a heterodyne RF experiment for bulk property measurement and a CW experiment for 3D imaging. In order to deal with large data size, a linear reconstruction algorithm that exploits separability of the inverse problem in Fourier domain is used for fast and memory-load-free reconstruction.

Multimodal information integration and visualization: optical imaging and MRI

We have developed a software platform for multimodal integration and visualization of diffuse optical tomography (DOT) and magnetic resonance imaging (MRI) of breast cancer. The image visualization platform allows multimodality 3D image visualization and manipulation of datasets, such as a variety of 3D rendering technique, and the ability to simultaneously control multiple fields of view. This platform enables quantitative and qualitative analysis of structural and functional diagnostic data, using both conventional & molecular imaging. The functional parameters, together with morphological parameters from MR can be suitably combined and correlated to the absolute diagnosis from histopathology. Fusion of the multimodal datasets will eventually lead to a significant improvement in the sensitivity and specificity of breast cancer detection. Fusion may also allow a priori structural information derived from MRI to be incorporated into the reconstruction of diffuse optical tomography images. We will present the early results of image visualization and registration on multimodal breast cancer data, DOT and MRI.

Differentiation of benign and malignant breast lesions by in-vivo three-dimensional diffuse optical tomography.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 AbstractsnnAbstract #805 nnBackground: Diffuse optical tomography (DOT) uses near-infrared light to non-invasively image total hemoglobin concentration and blood oxygen saturation in the human breast. Given its low cost, ease of use, and possibility of repeated measured over time, DOT is a promising adjunctive imaging modality for screening, diagnosis and monitoring of neoadjuvant therapy. In this study we explored the performance of DOT to differentiate benign and malignant breast lesions. Method and Materials: Forty-seven women with clinical or mammographic abnormalities were prospectively recruited for DOT. Most patients underwent gadolinium-enhanced MRI examination. Three-dimensional oxy-, deoxy-hemoglobin, total hemoglobin concentration, blood oxygen saturation and scattering coefficient images of each breast were reconstructed. Tumor-to-normal (T/N) ratios of these parameters were computed by defining tumor regions with guidance from MRI and radiology reports. In addition, optical index was constructed based on these parameters to maximize the T/N contrast. Only the biopsy-proven lesions were selected (51 breast lesions) and classified into three groups: benign lesions (N=10), malignant lesions where DOT preceded core biopsy (N=20) and malignant lesions where DOT was performed after core-biopsy (N=21). We fit a mixed effects model that estimated the mean optical T/N ratios and optical index for each group, and using the resulting standard errors developed 95% confidence intervals and tested the hypothesis that each optical contrast parameter was unity. Results: Malignant cancers showed statistically significant higher total hemoglobin concentration, scattering, oxy-hemoglobin concentration and optical index (P=0.01-0.04) compared to normal tissue. Furthermore, malignant lesions exhibited a two-fold average increase in an optical index derived from the endogenous optical parameters (95% CI: 1.4 - 2.4). To test whether bleeding due to core biopsy influence DOT results, we compared if there was statistically significant differences between two groups measured before or after core-biopsy. There were no statistically significant differences in these groups, suggesting that post biopsy hemorrhage did not alter the DOT results. Benign tumors did not show statistical significance in all of the T/N ratios. AUC of total hemoglobin concentration, scattering, oxy-hemoglobin and optical index suggested good discriminatory power with values between 0.90 and 0.99. Discussion: The data demonstrates the feasibility of differentiating benign and malignant lesions by quantitative three-dimensional DOT when the tumor location information is provided by other imaging modality. The main drawback of this study is the small number of benign lesions, which warrants further study. DOT technology is still at its developing stage and needs more investigation to find its niche in breast imaging.nnCitation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 805.

Joint analysis of non-concurrent magnetic resonance imaging and diffuse optical tomography of breast cancer

We have developed a novel method for combining non-concurrent MR and DOT data, which integrates advanced multimodal registration and segmentation algorithms within a well-defined workflow. The method requires little user interaction, is computationally efficient for practical applications, and enables joint MR/DOT analysis. The method presents additional advantages: More flexibility than integrated MR/DOT imaging systems, The ability to independently develop a standalone DOT system without the stringent limitations imposed by the MRI device environment, Enhancement of sensitivity and specificity for breast tumor detection, Combined analysis of structural and functional data, Enhancement of DOT data reconstruction through the use of MR-derived a priori structural information. We have conducted an initial patient study which asks an important question: how can functional information on a tumor obtained from DOT data be combined with the anatomy of that tumor derived from MRI data? The study confirms that tumor areas in the patient breasts exhibit significantly higher total hemoglobin concentration (THC) than their surroundings. The results show significance in intra-patient THC variations, and justify the use of our normalized difference measure defined as the distance from the average THC inside the breast, to the average THC inside the tumor volume in terms of the THC standard deviation inside the breast. This method contributes to the long-term goal of enabling standardized direct comparison of MRI and DOT and facilitating validation of DOT imaging methods in clinical studies.